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Innovative treatments for peritoneal metastatic cancer have attracted widespread attention from researchers. Here, we propose a drug-loaded nanomotor (PSBMA/l-Arg/DOX, PLD) based on zwitterionic materials for the treatment of peritoneal metastatic cancer through intraperitoneal injection. Zwitterionic polymer nanocarriers (PSBMA NPs) are obtained by radical polymerization with zwitterionic SBMA as the polymerization monomer and N,N'-Bis(acryloyl)cystamine (BAC) as the cross-linking agent. The zwitterionic substrate of this nanomotor has the ability to resist non-specific protein adsorption in ascites. The loaded l-arginine enables the nanomotor to have the ability to chemotaxis towards high concentrations of ROS/iNOS in tumors and be catalyzed to produce NO, achieving deep penetration into tumor tissue. Furthermore, the disulfide bond (SS) carried by the crosslinking agent used in the preparation of the nanomotor can respond to the high expression of reducing glutathione in the tumor microenvironment and undergo degradation, releasing a large amount of loaded drug DOX. Cell and animal disease model experiments confirme the good therapeutic effect of this drug-loaded nanomotor, providing new therapeutic concepts and strategies for the treatment of peritoneal metastatic cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Small extracellular vesicles (sEVs) have gained wide attention as efficient carriers for disease treatment. However, the proclivity of sEVs to be ingested by source cells is insufficient to accurately target specific sites, posing a challenge in realizing controlled targeting treatment. Here, we developed an engineered sEV nanocarrier capable of precise tumor targeting and enhanced synergistic therapy. Multivalent DNA probes, comprising abundant AS1411 aptamers and telomerase primers, were innovatively modified on the sEV membrane (M-D-sEV) for precise tumor targeting. To achieve synergistic therapy, gold nanorod-cerium oxide nanostructures (Au NRs-CeO 2 ) and manganese dioxide nanosheets-doxorubicin (MnO 2 NSs-DOX) were encapsulated into liposomes (Lip-Mat). Then M-D-sEV and Lip-Mat were fused together through membrane fusion to obtain nanocarriers. Owing to the multivalence of the probes, the surface of the nanocarriers was loaded with numerous aptamers, which greatly enhances their targeting ability and promotes the accumulation of drugs. When nanocarriers were ingested by tumor cells, telomerase and multivalent DNA probes triggered their aggregation, enhancing the therapeutic effect. Furthermore, under laser irradiation, Au NRs-CeO 2 converted light into hyperthermia, thereby inducing the destruction of nanocarriers membrane. This process initiated a series of reactions involving glutathione and H 2 O 2 consumption, as well as DOX release, ultimately achieving synergistic tumor therapy. In vitro and in vivo studies demonstrated the remarkable targeting ability of multivalent DNA probes and excellent therapeutic effect of this strategy. The engineered strategy of sEVs provide a promising approach for precise tumor therapy and hold great potential for the development of efficient, safe, and personalized drug delivery systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Using molecular hybridisation to develop conjugates of natural antitumor drugs is one of the research hotspots in recent drug development. In this study, β -anhydroicaritine with anticancer activity was conjugated to norcantharidine selectively to develop new antitumor lead candidates. In the condition of EDCI/DMAP/DCM, the C-3 and C-5 hydroxyl groups of β -anhydroicaritine was coupled with norcantharidin monoacid ester respectively, and the inhibitory activity of the synthesised conjugates against HepG2, MCF-7 and L-02 cells were tested by CCK-8 method. Most of these conjugates showed a better activity against HepG2 and MCF-7 cell lines compared to parent compound icaritin, but weaker than another parent compound norcantharidin.

The present study aimed to optimize a mouth-dissolving film (MDF) made from Pongamia pinnata stem bark extract to increase patient compliance and accelerate oral disease therapy. Several stem bark extracts were prepared, and karanjin was used as an herbal marker for the extracts. The ethanolic extract showed the maximum yield (12.10% ± 0.09%) and cytotoxic activity against human oral cancer (KB 3-1) and embryonic kidney cell lines. The MDF formulation was focused on incorporating a fixed amount of the extract and varying concentrations of HPMC E5 polymer, along with evaluating the performance of plasticizers like PEG 400 and propylene glycol (PG). An optimized formulation was determined based on disintegration time, wetting time, and folding endurance. The formulation consisted of HPMC E5 as a film-forming polymer, PG as a superior plasticizer, ascorbic acid as an antioxidant, and other ingredients contributing to solubility, dispersion, sweetening, and appearance. High-performance thin-layer chromatography-mass spectrometry analysis confirmed higher levels of karanjin in the optimized formulation, ensuring its successful incorporation and stability. Taste masking evaluations indicate a favorable taste profile and a high potential for patient compliance. The stability study displayed no significant changes in the physical characteristics of the film, affirming its stability and quality. In conclusion, the developed herbal-based optimized MDF presents a promising drug delivery system, offering enhanced patient compliance, taste masking, and stability. The MDF holds great potential for effective treatment and management of oral diseases, providing convenience and improved therapeutic outcomes., (© 2025 John Wiley & Sons Ltd.)

A new morphinan alkaloid (6 S , 9 S , 13  R , 14 S )-6-O-acetyl-7,8-Didehydro-4-hydroxy-3,7-dimethoxymorphinan-6-ol ( 1 ), and a new naturally occurring cularine alkaloid ( S )-2, 3, 12, 12a-tetrahydro-5, 6, 9, 10-tetramethoxy-1-methyl-1H-[1]benzoxepino[2, 3, 4- ij ]isoquinoline( 5 ), along with four known alkaloids were isolated from the roots of Stephania cepharantha . The structures of these compounds were elucidated based on spectroscopic data analyses. Cytotoxic activities of the compounds against three human cancer cell lines (A549, MCF-7 and SW480) were also evaluated.

Sonodynamic therapy (SDT) is a minimally invasive therapeutic approach that utilizes sonosensitizers to catalyze substrates and generate reactive oxygen species (ROS) under ultrasound stimulation, ultimately inducing tumor cell death. Enhancing the piezoelectric properties of nanomaterials and modulating the semiconductor energy band are effective strategies to improve the catalytic efficiency of sonosensitizers. In this study, we developed a two-dimensional (2D) copper-based piezoelectric metal-organic framework (MOF) sonosensitizer, denoted as CM, through the coordination of copper and dimethylimidazole. The unique 2D MOF structure imparts CM with piezoelectric characteristics, enabling it to enhance SDT efficacy by modulating the semiconductor bandgap and carrier mobility. Upon ultrasound irradiation, CM catalyzes oxygen to undergo a cascade reaction, producing highly toxic singlet oxygen. Additionally, cupric ions in CM can be reduced by glutathione, facilitating the spontaneous catalysis of hydrogen peroxide in tumors to generate hydroxyl radicals and deplete glutathione, thereby inducing oxidative damage. Moreover, cupric ions in CM can trigger tumor cell cuproptosis, which, in combination with the generated ROS, accelerates cell death. Thus, this study establishes a MOF-based system for controllably inducing multi-pathway cancer cell death and provides a foundation for enhancing ultrasound-catalyzed tumor therapy through the optimization of piezoelectric properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The anticancer potential of certain newly synthesized pyrazole and pyrazolopyridine derivatives has been estimated. NCI 60 cancer cells cytotoxic screening pointed out compounds 3e and 3f as the highest cytotoxic agents with % mean growth inhibition of 67.69% and 87.34%, respectively. The five dose outcomes outlined 3f as the most potent cytotoxic agent with promising MG-MID GI 50  = 3.3 µM when compared to erlotinib (MG-MID GI 50  = 7.68 µM). In the in vitro assays, compounds 3d, 3e, 3f, and 4a demonstrated dual inhibitory potential on EGFR WT and VEGFR-2 with IC 50 range of 0.066-0.184 µM and 0.102-0.418 µM, respectively. The best dual EGFR/VEGRF-2 inhibitory effect was shown by the compound 3f. Moreover, the latter compound stopped the cell cycle at the G1/S phase. Also, it greatly boosted total apoptosis, including early and late apoptosis, by 54.5- and 84.7-fold, respectively, which supposes HCT-116 cell death via inducing apoptosis. This was confirmed by the elevation of the BAX and caspase-3 levels, and the decreased BCL-2 level. Moreover, the safety of the most active compound 3f was assessed and the results showed promising selectivity of compound 3f toward HCT-116 over FHC (selectivity index [SI]: 20.84) when compared to erlotinib (SI: 3.42). Finally, compound 3f demonstrated efficient binding to both EGFR and VEGFR-2 enzymes, which could explain the sufficient inhibition level of each enzyme., (© 2025 Wiley Periodicals LLC.)

Here we present the biological properties of the arylbipyridine platinum (II) complex (arylbipy-Pt) and describe the potential mechanism of its antitumor action which differs from that of the well-known cisplatin. Leading to the oxidative stress and lipid peroxidation, the arylbipyridine platinum (II) complex showcases the significant cytotoxicity against the glioblastoma cells as shown by the MTT test. Using the 5-ethyl-2-deoxyuridine we study the proliferative activity of glioblastoma cells to affirm that arylbipyridine platinum (II) complex does not impede cell division or DNA replication. Staining by the MitoCLox dye and 2',7'-dichlorodihydrofluorescein diacetate demonstrates that the glioblastoma cells treated with arylbipy-Pt exhibit a strong increase of the lipid peroxidation and the stimulation of the reactive oxygen species formation. The hypothesis that arylbipy-Pt promotes oxidative death of tumor cells is confirmed by control experiments using N-acetyl-L-cysteine as an antioxidant. Further evidence for the oxidative mechanism of action is provided by real-time PCR, which shows high expression levels for genes associated with the heat shock proteins HSP27 and HSP70, which can be used as markers of tumor cell ferroptosis. To elucidate the chemical nature of the arylbipy-Pt complex activity, we perform 195 Pt NMR spectroscopy and cyclic voltammetry measurements under biologically relevant conditions. The results obtained clearly indicate the structural transformation of the arylbipy-Pt complex in the DMSO-saline mixture, which is crucial for its further antitumor activity via the oxidative pathway. The found correlation between the molecular structure of arylbipy-Pt and its effect on the tumor cell cycle paves the way for the rational design of Pt complexes possessing the alternative mechanism of antitumor activity as compared to DNA intercalation, providing possible solutions to the major problems such as toxicity and drug resistance., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

X-ray repair cross-complementing 2 (XRCC2), a critical protein in homologous recombination (HR), plays a significant role in the occurrence, progression, and drug resistance of colorectal cancer (CRC). In this study, a series of xanthohumol C derivatives were synthesized, and their anticancer activity was evaluated. The results revealed that A33 demonstrated the potent anticancer activity and effectively inhibited the proliferation of CRC cells in vitro. Mechanistic investigations revealed that A33 suppressed the transcription and expression of XRCC2, resulting in cell cycle delay and the accumulation of DNA damage, ultimately leading to cell proliferation inhibition. Furthermore, A33 displayed high safety, favorable bioavailability (F = 37.51 %), and potent tumor growth inhibition in vivo, which highlighting its potential as a candidate for the development of novel anti-CRC therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Aim: New phenyldiazene scaffold-linked heterocyclic pyrazole, pyrimidinone, pyrimidinthione, and/or triazine rings have been developed and synthesized., Methods & Results: Cytotoxicity of our derivatives was estimated on four cancer and VERO normal cell lines targeting EGFR T790M (epidermal growth factor receptor) and VEGFR-2 (vascular endothelial growth factor receptor-2) enzymes. Our new derivatives selectively inhibited both VEGFR-2 and EGFR as they have the essential structural requirements for inhibitors of both receptors. Derivative 14 was the most active on A549, HCT116, HepG2, and MCF-7 cancers with half-maximal inhibitory concentration (IC 50 ) = 5.50, 9.77, 7.12, and 7.85 µM respectively. The assessed derivatives 5 , 7 , 8, 9, 10, 12 and 14 showed IC 50  = 54.40-62.60 μM against normal VERO (normal kidney) cells with low toxicity. In addition, derivatives 14, 8, 10, 7 and 9 were discovered to be very good active inhibitors of VEGFR-2 at IC 50 values of 1.15, 1.35, 140, 1.78 and 1.90 µM, respectively. Furthermore, derivatives 14, 10, 8, and 9 strongly repressed EGFR T790M with IC 50  = 0.28, 0.33, 0.35, and 0.50 µM correspondingly. Additionally, the highly active compounds 8, 10, and 14 showed good ADMET profile., Conclusion: Our derivatives could be considered as anticancer agents with dual VEGFR-2 and EGFR T790M inhibition.

Targeting endoplasmic reticulum (ER) stress-induced apoptosis has attracted considerable research interest in anti-cancer drug development. Nur77 is a potential therapeutic target in many cancers and several Nur77 modulators have recently been identified as effective anticancer agents by activating ER stress. As an ongoing work, this study reports a new series of novel N 1 -(2-(adamantan-1-yl)-1H-indol-5-yl)-N 2 -(substituent)-1,2-dicarboxamides as potent Nur77 modulators that cause ER stress-induced apoptosis. Among this new series, most compounds show improved cytotoxicity against liver cancer (HepG2 and Huh7) and breast cancer (MCF-7 and MDA-MB-231) cell lines. The representative analog 15h dramatically induces Nur77 expression and cell apoptosis, showing excellent growth inhibition of HepG2 and MCF-7 cells (IC 50  < 5.0 μM). Mechanistically, 15h binds (K D  = 0.477 μM) and activates Nur77-mediated ER stress through the PERK-ATF4 and IRE1 signaling pathways, thereby inducing cell apoptosis. In vivo, 15h treatment strongly suppresses HepG2 xenograft tumor growth (tumor shrink by 54.06 %). In summary, we synthesize a series of novel indole derivatives, among which 15h has significantly improved pharmacological activity against various cancer cells. We further identify 15h as a novel ligand of Nur77, which may serve a therapeutic lead for developing new cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Endophytic actinomycetes exhibit considerable potential for the production of biologically active metabolites due to their coevolution with plant hosts. In this study, an endophytic Streptomyces chartreusis M7 was isolated from Houttuynia cordata Thunb. Bioactivity-guided investigation of the metabolites produced by this strain led to the identification of thirteen anthracycline-derived polyketides, including five unreported anthraquinones designated streptoquinones A-E (1-5) and two undescribed angular polyketides named chartins A and B (6-7) along with six knowns. Their structures were elucidated through comprehensive spectroscopic analysis and ECD calculations. Notably, chartins A (6) and B (7) feature angular tetracyclic and pentacyclic skeletons, respectively, which have undergone several oxidative rearrangements. Moreover, streptoquinone A (1) exhibited moderate cytotoxicity against A549 cells, with an IC 50 value of 4.8 μM., Competing Interests: Declaration of competing interest I (Yi Shuang Wang) declare that we have no known competing financial interests or personal relationships that could have appeared to influence the manuscript titled “Discovery of new anthracycline-derived polyketides with antitumor activity from endophytic Streptomyces sp. M7” submitted to Phytochemistry. I certify that I have read and understand the Phytochemistry conflict of interest policy, and I also understand that failure to disclose a conflict of interest may result in the manuscript being rejected or retracted. I understand that this information will be subject to peer review, and I am willing to provide further information if required. I confirm that we have no known conflicts of interest that would influence the results or interpretation of the data presented in this manuscript., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Peptidyl-prolyl cis/trans isomerase Pin1 occupies a prominent role in preventing the development of certain malignant tumors. Pin1 is considered a target for the treatment of related malignant tumors, so the identification of novel Pin1 inhibitors is particularly urgent. In this study, we preliminarily predicted eight candidates from FDA-approved drug database as the potential Pin1 inhibitors through virtual screening combined with empirical screening. Therefore, we selected these eight candidates and tested their binding affinity and inhibitory activity against Pin1 using fluorescence titration and PPIase activity assays, respectively. Subsequently, we found that four FDA-approved drugs showed good binding affinities and inhibition effects. In addition, we also observed that bexarotene can reduce cell viability in a dose-dependent and time-dependent manner and induce apoptosis. Finally, we inferred that residues K63, R68 and R69 are important in the binding process between bexarotene and Pin1. All in all, repurposing of FDA-approved drugs to inhibit Pin1 may provide a promising insight into the identification and development of new treatments for certain malignant tumors., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Here ginsenoside Rg1 was used to synthesise Rg1 carbon nanodots via a one-step hydrothermal method. The surface of the Rg1 carbon nanodots is rich in hydrophilic functional groups with good water solubility and biocompatibility. The Rg1 carbon nanodots exhibited a high inhibitory effect on the proliferation, migration, and proapoptotic ability of non-small cell lung cancer A549 cells. The changes in the levels of ROS, Ca 2+ , and MMP in A549 cells after the administration of Rg1 carbon nanodots were evaluated and further correlated with relevant proteins in the caspase apoptotic pathway. Proteomic screening revealed that the Rg1 carbon nanodots could regulate A549 cell apoptosis by activating the expression of MAPK pathway-related proteins. In the in vivo experiment, the therapeutic efficacy of the Rg1 carbon nanodots in inhibiting tumour growth was much higher than that of commonly used chemotherapy drugs, with negligible toxicity and side effects. Immunohistochemical staining showed that the expression of caspase- and MAPK pathway-related proteins in mouse tumour tissues was consistent with that at the cellular level. The results suggest that Rg1 carbon nanodots can promote tumour apoptosis and represent a potential therapeutic agent for human non-small-cell lung cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Four isoprenylated flavonols, including two new compounds, macainermisins A-B ( 1 - 2 ), and two known compounds, sinoflavonoid P ( 3 ), broussoflavonol F ( 4 ), were isolated from the leaves of Macaranga inermis . A combination of HRESIMS, UV, 1D, and 2D NMR spectra elucidated the structures of 1 - 2 . Flavonols ( 1 - 4 ) were evaluated against three cancer cells. Compound 1 showed high cytotoxicity against WiDR with an IC 50 value of 0.93 µM, and compound 2 was active towards HeLa and WiDR (IC 50 values of 0.90 and 0.94 µM), and compound 3 showed high activity towards 4T1 and HeLa (IC 50 values of 0.83 and 0.98 µM).

Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited therapeutic options, often exhibiting resistance to standard radiotherapy (RT) and chemotherapy. Recent advancements in nanomedicine provide an opportunity to enhance treatment efficacy through innovative drug delivery systems and radiosensitizers. In this study, we present a novel nanotheranostic platform, MOs-G@DOX, engineered to enhance the therapeutic efficacy of RT in the treatment of TNBC. This platform consists of gadolinium-containing mesoporous organosilica nanoparticles (MOs-G) that serve a dual function as a drug carrier and a radiosensitizer. The MOs-G were synthesized via a surfactant-mediated sol-gel process, followed by gadolinium incorporation through nanoprecipitation. The antitumor drug doxorubicin (DOX) was subsequently loaded into the mesoporous structure, forming the MOs-G@DOX nanoplatform. Comprehensive in vitro and in vivo studies demonstrated that MOs-G@DOX exhibits excellent biocompatibility and significantly enhances the radiosensitivity of TNBC cells, leading to superior tumor growth inhibition compared to conventional treatments. The stability of MOs-G, with minimal gadolinium ion leakage, further underscores its potential as a safe and effective nanomedicine. Additionally, the combination of MOs-G@DOX with RT showed a marked increase in reactive oxygen species (ROS) generation and tumor cell apoptosis, which were confirmed through histological analyses. These findings suggest that MOs-G@DOX is a promising candidate for advancing cancer therapy, particularly in the context of RT for TNBC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Improving drug delivery efficacy is the key point for enhancing the therapeutic index of medicines. Herein, we report fatty chain conjugated paclitaxel (PTX) prodrugs with a disulfide bond as linker. The formed prodrugs can self-assemble into stable nanoparticles in aqueous solutions, and rapidly transform into long-circulating nanocomplexes via the non-covalent binding to serum albumin in blood, enabling efficient drug delivery and robust antitumor effect. PTX prodrug (PC) with single-chain possess the improved self-assembly and interaction with albumins. The formed PC@albumin nanocomplexes reinforce the responsiveness of prodrug activation, and exhibit the enhanced tumor suppression ability. This strategy of hitchhiking albumin to deliver therapeutic agents holds great promise for enhanced chemotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Benzofuropyridines (BFP) are polycyclic compounds with known applications in neuronal diseases. However, its derivatization patterns and anticancer potential remains unexplored. Leveraging the idea of diversity-oriented synthesis (DOS), we developed a highly efficient synthetic route for BFP, to increase the library of available analogs producing three compounds in one reaction set up, including the 2O-, 6O-, and the 1 N-substituted species, also synthesizing the unusual 2-pyridone derivatives. Key bromination reaction of the BFP moiety was successfully described which can widen the available variation in the compound's structure. The cytotoxic activity of the compounds was assessed against SH-SY5Y (neuroblastoma), HepG2 (hepatocellular carcinoma), Kb (human oral epidermoid), HeLa (cervical) and MCF-7 (breast) cancer cell lines. In the series, the m-bromobenzyl (5 b), methylcyano (5 g) and propargyl (5 h) 2O-derivatives demonstrated good selectivity against cancer cells with selectivity index (SI) of >71 for 5 g against HeLa over the normal cells, as compared to the standard drug, Doxorubicin (SI=6.7). The quantitative structure-activity relationship (QSAR) analysis revealed an impressive correlation of the defined descriptors with the bioactivity having an R 2 value of 0.971 and 0.893 for Kb and HeLa respectively. Altogether, our work highlighted new information on the synthesis of BFP derivatives with potent cytotoxic activity., (© 2024 Wiley-VCH GmbH.)

The utilization or improvement of tumor microenvironment (TME) has become a breakthrough in emerging oncology therapies. To address the limited therapeutic efficacy of single modality, a multi-functional integrated nanoplatform based on a TME-responsive PtAu/MnO 2 cascade nanoreactor with multi-enzymatic activities was developed for multimodal synergistic tumor therapy. Benefiting from the slightly acidic environment and high-level glutathione (GSH) in TME, PtAu/MnO 2 cascade nanoreactor consumed GSH, followed by the reductive generation of manganese ion (Mn 2+ ) and the release of PtAu nanoparticles (NPs). Then, the multimodal synergistic tumor therapy was activated as follows. First, GSH depletion inhibited the activity of glutathione peroxidase 4 and led to the accumulation of lipid peroxidation, thereby inducing tumor cell ferroptosis. Second, PtAu NPs exhibited catalase-like, glucose oxidase-like and nicotinamide adenine dinucleotide (NADH) oxidase-like activities, which generated oxygen for the cascade reaction to alleviate hypoxia and further depleted glucose, NADH and adenosine triphosphate, leading to the inhibition of tumor cell proliferation via starvation therapy. Third, the production of reactive oxygen species by the oxidase- and peroxidase-like activities of PtAu NPs and the Fenton-like reaction of Mn 2+ simultaneously induced tumor cell apoptosis via chemodynamic therapy. Briefly, the in vitro and in vivo results confirmed that the multi-functional integrated nanoplatform based on a PtAu/MnO 2 cascade nanoreactor with five nanozyme activities demonstrated outstanding biocompatibility and greater inhibition of tumor growth via synergistic ferroptosis/starvation therapy/apoptosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Novel pH-sensitive polymeric photosensitizer carriers from the phthalocyanine (Pc) group were investigated as potential photodynamic therapy drugs for the treatment of breast cancer. Their high antiproliferative activity was confirmed by photocytotoxicity studies, which indicated their high efficacy and specificity toward the SK-BR-3 cell line. Importantly, the Pcs encapsulated in the polymeric nanoparticle (NP) carrier exhibited a much better penetration into the acidic environment of tumor cells than their free form. The investigated Pc4-NPs and TT1-NPs exhibited a high selectivity to healthy fibroblasts as well as non-toxicity without irradiation. This paper describes the detailed mechanism of action of the evaluated compounds by measuring reactive oxygen species (ROS), including singlet oxygen; imaging cellular localization; and analyzing key signaling pathway proteins. An additional advantage of the evaluated compounds is their ability to inhibit the Akt protein expression, including its phosphorylation, which the Western blot test confirmed. This is particularly important because breast cancers often overexpress the HER-2 receptor-related signaling proteins. Moreover, an analysis of proteins such as GLUT-1, HO-1, phospho-p42/44, and BID revealed the significant involvement of ROS in disrupting cellular homeostasis, thereby leading to the induction of oxidative stress and resulting in apoptotic cell death., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

In the current study, a novel series of 1,2,4-oxadiazoles were designed, synthesized, and evaluated for their biological activities. A cell-based antiproliferative screening was accomplished on the newly synthesized 1,2,4-oxadiazoles along with our previously reported aryl(alkyl)azoles (AAAs) containing middle heterocyclic cores thiazole and oxazole. Among the tested compounds, naphthyl- thiazoles demonstrated higher antiproliferative activity and B3 was identified as the most potent compound with IC 50 values in the range of 2.03-3.6 µM against SH-SY5Y neuroblastoma, HT-29 colorectal adenocarcinoma, and fibroblast cells (ten folds more potent than 5-FU and irinotecan). Further investigation revealed that B3 strongly inhibits tubulin polymerization with an IC 50 of 0.79 µM, outperforming the reference drug colchicine (IC 50  = 1.46 µM). In addition, evaluation of B3 on the expression level of BAX, BCL2, and CYCLIN D1 genes indicated the suppression of the cell cycle in the genome level. Interestingly, the 1,2,4-oxadiazole congeners displayed optimal anticonvulsant activity with significantly reduced cytotoxicity. Among the oxadiazole series, compound D4 featuring a 1,2,4-triazole head group demonstrated the highest activity in the maximal electroshock (MES) and pentylenetetrazol (PTZ) tests, with ED 50 values of 2.23 and 24.60 mg/kg, respectively. In vivo evaluations suggested that D4 exerts its anticonvulsant effects by enhancing GABA A currents. In conclusion, our findings indicated that B3 in the thiazole congeners is a promising drug candidate for cancer treatment with a well-defined mechanism of action. Moreover, D4 and its congeners containing oxadiazole core are much safer anti-seizures which have potential for preclinical considerations as novel anticonvulsants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Triple-negative breast cancer (TNBC) represents a highly malignant subtype of breast cancer with limited therapeutic options. In this study, we designed and synthesized a series of 1,4-DHP derivatives by structure-based strategy, 43 was documented to be a potent SIRT3 activator and exhibited profound anti-proliferative activity in BT-549 and MDA-MB-231 cells with low toxicity over normal cells. Additionally, 43 displayed the ability of direct binding to SIRT3 with a K d value of 51.51 μM in BLI assay, and the potential bonding mode was elucidated through molecular docking. 43 could inhibit the proliferation, migration, and glycolysis, induced mitochondrial membrane potential decreased and apoptosis in BT-549 and MDA-MB-231 cells. Collectively, these results demonstrate that 43 is a potent SIRT3 activator with the potential to anti-TNBC through signaling pathways regulated by SIRT3., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Seeking new drug candidates among compounds of natural origin is an effective and widely used method of fighting various diseases, especially cancer. Lasalocid acid is one of the naturally occurring polyether ionophore antibiotics, which also exhibits interesting anticancer activity. Therefore, to expand the knowledge about the anticancer properties of lasalocid derivatives, a series of its new amides were synthesized and their antiproliferative activity against cancer cell lines was studied. Amides 7-9 with an aromatic substituent, displayed potent antiproliferative activity (IC 50 : 0.84-5.18 μM) and demonstrated a good selectivity index (SI: 1.4-15.3). Furthermore, almost all of lasalocid amides overcame the drug resistance of the doxorubicin-resistant cancer cell line (LoVo/DX). Because the biological activity of ionophores is strictly connected with their ability to transport the Na + cation through lipid bilayers, the crystal structure of the complex of compound 8 with the Na + cation was resolved. Lasalocid amides exhibit a pseudocyclic structure and are able to coordinate the Na + cation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Photodynamic therapy (PDT) is an emerging cancer therapy known for its non-invasive approach and minimal side effects. However, the clinical effectiveness of PDT is limited by the poor distribution and penetration of photosensitizers (PS) in tumors. In this research, we developed a novel delivery system for PS, termed EWC, using the facultative probiotic Escherichia coli Nissle 1917 (EcN) as a carrier. Chlorin e6 (Ce6) was electrostatically adsorbed onto the surface of EcN with the assistance of water-soluble chitosan (WCS). EWC demonstrated effective photodynamic activity and was readily internalized by human lung cancer cells (A549). In vitro assays confirmed its low toxicity to mammalian cells and potent photodynamic cytotoxicity against A549 cells. Additionally, EWC penetrated tumor spheroids and inhibited their growth, as shown by 3D fluorescence imaging. In vivo tests revealed that EWC enhanced the distribution and accumulation of Ce6 at the tumor site, effectively inhibiting tumor growth under light stimulation. Moreover, EWC exhibited excellent biocompatibility in mice. This facultative probiotics-based delivery system significantly improves the efficiency of PDT, offering a promising approach for low-toxicity and high-efficiency tumor therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/aim: Flavonoids are a large group of naturally occurring compounds with a wide range of biological properties and thus they represent a privileged scaffold in medicinal chemistry. We designed and synthesized a series of polymethoxylated 3-styrylflavones as a novel class of styryl-bearing flavone compounds., Materials and Methods: 3-Styrylflavones were systematically synthesized using Wittig reaction between various benzaldehyde derivatives and polymethoxylated 3-(bromomethyl)flavones, and evaluated their antiproliferative activity against HL60., Results: Among the compounds synthesized, 2',3',4'-trimethoxy-3-(E)-styrylflavone (IC 50 =68 μM) and 2',3',3‴,4',4‴,5‴-hexamethoxy-3-(E)-styrylflavone (IC 50 =92 μM) demonstrated potent anti-proliferative activity., Conclusion: Introduction of 3-styryl substituent in 3-methylflavone increased the antiproliferative activity. Structure-activity relationship studies and theoretical calculations indicated the importance of 2',3',4'-trimethoxy-phenyl substituent in enhancing the activity., (Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Triple-negative breast cancer (TNBC) has short survival rates. This study aimed to prepare a novel formula of sorafenib, carbon nanotubes (CNTs), and folic acid to be tested as a drug delivery system targeting versus TNBC compared with free sorafenib and to evaluate the formula stability, in vitro pharmacodynamic, and in vivo pharmacokinetic properties. The formula preparation was done by the synthesis of polyethylene glycol bis amine linker, CNT PEGylation, folic acid attachment, and sorafenib loading. The prepared formula has been characterized using X-ray diffraction, Flourier-transform infrared, 1 HNMR, UV, high resolution-transmission electron microscope, field emission scanning electron microscopy, and Zeta potential. In vitro studies included drug release determination, MTT assay, flow cytometry to determine the apoptotic stage with percent, cell cycle analysis, and apoptotic marker assays for caspase-3, 8, 9, cytochrome c, and BCL-2. The in vivo study was performed to determine bioavailability and half-life in rats. The in vitro MTT antiproliferative assay revealed that the formula was threefold more cytotoxic toward TNBC cells than free sorafenib, and the flow cytometry showed a significant increase in apoptosis and necrosis. The formula has a greater inhibitory effect on BCL-2 and a lessening effect on cytochrome c and caspases 3, 8, and 9 than free sorafenib. In vivo experiments proved that our novel formula was superior to free sorafenib by increasing bioavailability by eight times and prolonging the half-life by three times. These results confirmed the successful preparation of the desired formula with better pharmacodynamic and pharmacokinetic properties. These promising results may show a novel therapeutic strategy for TNBC patients., (© 2024 International Union of Biochemistry and Molecular Biology, Inc.)

The tumor microenvironment (TME) exhibits characteristics such as hypoxia, weak acidity, and enrichment of glutathione and hydrogen peroxide (H 2 O 2 ), which greatly limits the effectiveness of tumor magnetic resonance imaging (MRI) and photodynamic therapy (PDT). Carbon dots (CDs) nanozymes are excellent candidate materials with both diagnostic and therapeutic potential. However, CDs nanozymes with both ultra-high relaxation rate and good therapeutic effect are still to be developed. Herein, novel carbon dots (MPC-CDs) were synthesized from polyethyleneimine (PEI), the photosensitizer hexahydroporphyrin (Ce6) and manganese. The Ce6 enabled the MPC-CDs to exhibit excellent PDT therapeutic ability, with a singlet oxygen yield as high as 1.52. The doping of the metal manganese gave the complexes CAT-like activity, and the singlet oxygen rate was further increased in the presence of H 2 O 2 , up to 1.97. In addition, manganese endowed the CDs with better MRI capabilities, and the r 1 and r 2 relaxation rates were significantly improved by 7.8-fold and 4.6-fold under acidic and H 2 O 2 conditions. The in vitro and in vivo results showed that MPC-CDs could achieve TME-responsive MR imaging and synergistic anti-tumor effects, providing an effective strategy to further enhance the effectiveness of tumor diagnosis and treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Twelve neomanoalide derivatives (1-12) and two halisulfate derivatives (13 and 14), nine of which are unprecedented (4-9, 11, 12, and 14; coscilides A-H and halisulfate 11, respectively), were isolated from the sponge Coscinoderma bakusi. The previously unreported neomanoalide derivatives show distinct features in their 6,7-double bond geometry (4 and 9) or terpenoid moieties (5-8, 11, and 12) compared to the reported ones, as elucidated using NMR spectroscopy and HRMS analysis. Among these derivatives, compounds 11 and 12 contain terpenoid moieties that are rarely found in marine natural products. The isolated compounds showed low activity against hTRPA1, six pathogenic bacterial strains, 10 cancer cell lines, except in the case of 7, which exhibited activity against hTRPA1 (IC 50 , 34.5 μM) and Staphylococcus aureus (MIC, 32.0 μg/mL). The halisulfate derivative 14 inhibited NO production in LPS-activated RAW 246.7 macrophage by 45% at a concentration of 10.0 μM. Although no significant activity was observed for the compounds in this study, the compounds reported herein would contribute to the chemical diversity of marine sesterterpenoids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this study, we aim to detail the design and synthesis of a series of benzothiazole tethered triazole compounds that incorporate acetamide chains, with the purpose of investigating their potential as anticancer agents. The structural integrity of the compounds was confirmed through characterization using 1 H NMR, 13 C NMR, mass spectrometry, and IR spectroscopy. The compounds demonstrated notable cytotoxic effects when tested against a range of cancer cell lines, with a specific inhibition observed in triple-negative breast cancer. Among the compounds, the one with trichloro substitution demonstrated the highest potency, as indicated by an IC 50 value of 30.49 μM. The compounds were found to trigger cell cycle arrest in the G2/M phase and promote apoptosis, as observed in the mechanistic studies. The Bcl-2 protein exhibited significant binding interactions in molecular docking studies, which were then corroborated through molecular dynamics simulations spanning 100 ns. The simulations confirmed the stability of the ligand-protein complex, as supported by RMSD, RMSF, and hydrogen bond analyses, reinforcing the proposed mechanism of Bcl-2-mediated apoptosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

This study involves the design, divergent synthesis, conformational and structural analysis, target prediction, and molecular docking simulations of novel nano N-thiazolylpyridylamines 2-7 and 10 as potential cyclin-dependent kinase 2 (CDK2) inhibitors. Using a divergent synthesis approach, the compounds were designed with structural variation and optimization in mind. The conformational and structural properties were explored through various spectroscopic techniques, confirming the structure, stability, and preferred conformations. Additionally, nanocrystalline characterization, including X-ray diffraction analysis, revealed the nanoscale structural features of the synthesized molecules. Most compounds exhibited a crystalline nature with crystallite sizes ranging from 10.75 to 57.77 nm, which is crucial for improving cellular uptake and anticancer efficacy. Biological testing was performed to evaluate the cytotoxicity of compounds 2-7 and 10 against cancer cell lines, including HepG2, MCF-7, and HCT-116. Compound 5 exhibited significant cytotoxicity with IC 50 values of 10.9 ± 0.5 μM, 6.98 ± 0.3 μM, and 6.3 ± 0.2 μM against MCF-7, HePG2, and HCT116, respectively. Other compounds demonstrated varied activities, with compounds 4, 6, and 10 showing moderate activity against the MCF-7 cell line. Computational techniques suggested a strong probability of these compounds targeting CDK2, with molecular docking and dynamics used to predict their binding mechanisms. These findings suggest that N-thiazolylpyridylamines may serve as new anticancer agents for further lead optimization., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Samir Bondock reports financial support was provided by King Khalid University. Samir Bondock reports a relationship with King Khalid University that includes: employment. The authors have declared no conflict of interest If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Surgical risk and wound area can be reduced by diminishing tumor volume before surgery. The chemotherapy and radiotherapy currently used that can reduce the tumor volume generally cause severe systemic side effects. Phototherapy has recently emerged as an effective treatment modality for superficial cancers. However, phototherapy is limited by the low utilization of photosensitizer, the tumor hypoxia, and the low photothermal conversion efficiency. Herein, we report the cancer membrane biomimetic nanoparticles assembled by Chlorin e6 (Ce6) and chlorambucil (CRB). Ce6@CRB nanoparticles (CCNPs) show excellent photothermal conversion efficiency, which is 2 times higher than free Ce6. Meanwhile, CCNPs can produce singlet oxygen stably compared to free Ce6 thereby reducing the dependence on oxygen. Furthermore, the coating of 4 T1 cancer membrane on the surface of CCNPs endows them with the ability of homologous targeting, not only improving the utilization of Ce6, but also effectively activating the immune system in vivo when combined photodynamic therapy (PDT) and photothermal therapy (PTT). Intriguingly, surgical resection is performed after phototherapy in this treatment regimen, which can effectively reduce the wound area. Together, this work provided a feasible and creative method for tumor clinical therapy for its patient-centric and humanitarian focus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

EGFR inhibitors are a class of targeted therapies utilized in the management of certain tumor kinds such as NSCLC and breast cancer. Series of 1,2,3-triazole-Schiff's base hybrids were designed, synthesized, and estimated for their antitumor effect toward breast cancer cells, MCF-7 and MDA-MB-231. The safety and selectivity of the new compounds were tested using normal cell (WI-38). Analogs 4a, 4b, and 5f demonstrated significant antitumor effects toward both MCF-7 and MDA-MB-231 with IC 50 range of 5.61-18.01 µM in comparison to Doxorubicin (6.72 µM). Moreover, they proved considerable selectivity toward the tested cancer cells (SI values of 4.36-5.33). The superior compounds were investigated for EGFR inhibition where compounds 4b and 5f showed the highest EGFR inhibition effect with IC 50 equal 0.16 and 0.15 µM, respectively utilizing Gefitinib as reference (IC 50  = 0.081 µM). Further mechanistic studies for hybrid 5f in MDA-MB-231 cells, exhibited cell cycle arrest at G2/M phase by 29.85 % that was accompanied by the elevation of apoptosis percent by 48-fold more than the control. The apoptosis studies indicated that hybrid 5f was able to upregulate Bax (9.43 folds) while downregulate Bcl-2 (0.27) with substantial remarkable elevation of Bax/Bcl-2 ratio (35:1). Furthermore, it upregulated both caspases 8 and 9 by 2.93 and 6.54-fold, respectively. Molecular modeling studies showed the good binding affinity of compounds 4b and 5f with EGFR kinase active site explaining their potent biological effects. Drug likeness and ADMET features of compounds 4b and 5f demonstrated that they represent promising drug like candidates against breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Chemical investigation of the native medicinal plant Tabernaemontana bovina led to the isolation of five previously unreported monoterpenoid indole alkaloids tabernovinaines A-E (1-5) together with twenty-seven known analogs (6-32), including a bisindole alkaloid 1 with the (E)-4-aminobut-3-en-2-one fragment, as well as a unique cage skeleton 2 containing 6/5/8/6/6 ring system. The chemical structures of these unreported compounds were elucidated using mass spectrometry, NMR spectroscopy, circular dichroism, density functional theory calculations, and derivatizations. The activity evaluation shows that the bisindole alkaloid 1 revealed a potential cytotoxic effect by inducing HepG2 cell apoptosis and damaging clonal sphere expansion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Gynecological tumors are highly aggressive cancers in women, often treated with conventional treatments that can cause significant side effects. This study focuses on the preparation of chitosan nanoparticles from Nyctanthes arbor-tristis leaves, which possess anti-tumor properties, to address and overcome these issues. The successfully synthesized nanoparticles were characterized by UV-spectroscopy, DLS, TEM, and FTIR spectroscopy to analyze their physiochemical properties. In vitro studies, including cytotoxicity and scratch wound healing assays, along with staining and qRT-PCR, revealed the nanoparticles' anticancer efficacy against breast and ovarian cancer cells. The formation of Nat-CSNPs showed an absorbance peak at 221 nm, a particle size range of 41-56 nm with a spherical shape, polydispersity, and a positive surface charge. FTIR spectroscopy demonstrated the presence of functional groups associated with the synthesized Nat-CSNPs. It exhibited dose-dependent cytotoxicity, with IC 50 values of 62.40 μg/ml for MDA-MB-231 and 44.7 μg/ml for SKOV3 cells. Further assays such as wound healing assay, and DAPI/AO/EtBr staining demonstrated their antiproliferative and apoptotic effects on MDA-MB-231 and SKOV3 cells. Induction of apoptosis by the chitosan-nanoparticle via upregulation of the pro-apoptotic genes (Bax, Cas3, Cas9) and downregulation of antiapoptotic genes (Bcl2) was assessed using qRT-PCR analysis. In vivo acute toxicity assessments of Nat-CSNPs on Danio rerio revealed no significant impact on glucose levels or AST, ALT, and AChE activity, indicating low toxicity. These findings underscore the potent anticancer effects of Nat-CSNPs, particularly inducing apoptosis in MDA-MB-231 and SKOV3 cell lines. While demonstrating low toxicity in Danio rerio, Nat-CSNPs are considered a promising novel anti-cancer drug for breast and ovarian cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Five series of new 1,3,4-thiadiazole hybrids were designed and synthesized as promising EGFR inhibitors. Three human cancer cell lines were employed for testing each hybrid's in vitro antiproliferative efficacy; colon HCT-116, liver HepG-2 and breast MCF-7 using MTT assay. Comparing compound 9a to the reference doxorubicin, 9a shown superior activity to that of Dox with respect to MCF-7 (IC 50 3.31 µM) while being secure for normal cells WI-38 (IC 50  = 43.99 µM). Further evaluation of the EGFR inhibitory activity of the most active candidates-4a, 6b, 8b, 9a, and 9 d-was performed. Of them, compounds 9a and 8b demonstrated the highest IC 50 values, 0.08 and 0.15 µM, respectively, relative to the reference gefitinib (IC 50  = 0.04 µM). Subsequent mechanistic analysis of compound 9a revealed a notable 14.24-fold increase in overall apoptosis and a 28.92% cell cycle arrest at G2/M. Additionally, research on apoptosis demonstrated that it triggered the mitochondrial apoptotic pathway. In MCF-7 cells, it also led to an increase in ROS buildup. For the most powerful EGFR inhibitors, 9a and 8b, a molecular docking research was conducted, and all of the findings agreed with the biological findings., (© 2024 Wiley Periodicals LLC.)

Pancreatic ductal adenocarcinoma (PDAC) has limited treatment options, emphasizing the urgent need for effective therapies. The predominant driver in PDAC is mutated KRAS proto-oncogene, KRA, present in 90% of patients. The emergence of direct KRAS inhibitors presents a promising avenue for treatment, particularly those targeting the KRAS G12C mutated allele, which show encouraging results in clinical trials. However, the development of resistance necessitates exploring potent combination therapies. Our objective was to identify effective KRAS G12C -inhibitor combination therapies through unbiased drug screening. Results revealed synergistic effects with son of sevenless homolog 1 (SOS1) inhibitors, tyrosine-protein phosphatase non-receptor type 11 (PTPN11)/Src homology region 2 domain-containing phosphatase-2 (SHP2) inhibitors, and broad-spectrum multi-kinase inhibitors. Validation in a novel and unique KRAS G12C -mutated patient-derived organoid model confirmed the described hits from the screening experiment. Our findings propose strategies to enhance KRAS G12C -inhibitor efficacy, guiding clinical trial design and molecular tumor boards., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Two new alkaloids, Aspera chaetominines A ( 1 ) and B ( 2 ), a new derivative ( 3 ) of terrein, and together with 11 known compounds ( 4-14 ) were isolated from marine sponge Callyspongia sp. -derived fungus Aspergillus versicolour SCSIO XWS04 F52, which was identified on the basis of morphology and ITS sequence analysis. The planar structures of 1-3 were determined by spectroscopic ( 1 H, 13 C NMR, HSQC, HMBC, and 1 H- 1 H COSY), and MS analysis. Compounds 1 and 2 showed cytotoxic activity against leukaemia K562 and colon cancer cells SW1116 with IC 50 7.5 to 12.5  μ M, and also compounds 1 and 2 exhibited significant protection against H1N1 virus-induced cytopathogenicity in MDCK cells with IC 50 values of 15.5 and 24.5  μ M, respectively.

To discover new Werner (WRN) helicase inhibitors, a series of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives were designed and synthesized through a structural optimization strategy, and the anticancer activities of 25 new target compounds against PC3, K562, and HeLa cell lines were evaluated by the MTT assay. Some of these compounds exhibited excellent inhibitory activity against three different cancer cell lines. Compounds 6a, 8i, and 13a showed better antiproliferative activity against K562 cells, with IC 50 values of 3871.5, 613.6 and 134.7 nM, respectively, than did paclitaxel (35.6 nM), doxorubicin (2689.0 nM), and NSC 617145 (20.3 nM). To further verify whether the antiproliferative activity of these compounds is dependent on WRN, PC3 cells overexpressing WRN (PC3-WRN) were constructed to further study their antiproliferative potency in vitro, and the inhibition ratio and IC 20 values showed that compounds 6a, 8i, and 13a were more sensitive to PC3-WRN than were the control group cells (PC3-NC). The IC 20 ratios of compounds 6a, 8i, and 13a to PC3-NC and PC3-WRN were 94.3, 153.4 and 505.5, respectively. According to the docking results, the compounds 6a, 8i, and 13a overlapped well with the binding pocket of 6YHR. Further study demonstrated that among the tested compounds, 13a was the most sensitive to PC3-WRN. In summary, our research identified a series of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives as potential WRN-dependent anticancer agents., Competing Interests: Declarations. Conflict of interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Medullary thyroid cancer (MTC) is a highly aggressive and chemotherapy-resistant cancer originating from the thyroid's parafollicular C cells. Due to its resistance to conventional treatments, alternative therapies such as boric acid have been explored. Boric acid, a boron-based compound, has shown anticarcinogenic effects, positioning it as a potential treatment option for MTC. TT medullary thyroid carcinoma cell line (TT cells) and human thyroid fibroblast (HThF cells) were utilized for the cell culture experiments. Cell viability was assessed using the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. Total RNA was extracted using Trizol reagent for gene expression and microRNA (miRNA) analysis via reverse transcription-polymerase chain reaction (RT-PCR). The extent of apoptosis induced by boric acid was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Colony formation assays were conducted to evaluate the impact of boric acid on the colony-forming ability of MTC cells. At 48 h, 50% inhibitory concentration (IC50) of boric acid was found to be 35 μM. Treatment with boric acid resulted in significant modulation of apoptosis-related genes and miRNAs, including increased expression of phorbol-12-myristate-13-acetate-induced protein 1(NOXA), apoptotic protease activating factor 1 (APAF-1), Bcl-2-associated X protein (Bax), caspase-3, and caspase-9. In contrast, the expression of B cell lymphoma 2 (Bcl2), B cell lymphoma- extra-large (Bcl-xl), and microRNA-21 (miR-21), which are linked to the aggressiveness of MTC, was significantly reduced. The TUNEL assay indicated a 14% apoptosis rate, and there was a 67.9% reduction in colony formation, as shown by the colony formation assay. Our study suggests that boric acid may have anticancer activity in MTC by modulating apoptotic pathways. These findings suggest that boric acid could be a potential therapeutic agent for MTC and possibly for other malignancies with similar pathogenic mechanisms., Competing Interests: Declarations. Ethics Approval: TT (ATCC, CRL 1803TM) and HThF (ScienCell Cat No: 3730) cell lines, which provide de-identified samples ,were used in this study,. This study was reviewed and deemed exempt by our Pamukkale Univercity Institutional Review Board. The BioBank protocols are in accordance with the ethical standards of our institution and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Conflict of Interest: The authors declare no competing interests., (© 2024. The Author(s).)

Dysregulation of the fibroblast growth factor receptor 1 (FGFR1) signaling has prompted efforts to develop therapeutic agents, which is a carcinogenic driver of many cancers, including breast, prostate, bladder, and chronic myeloid leukemia. Despite significant progress in the development of potent and selective FGFR inhibitors, the long-term efficacy of these drugs in cancer therapy has been hampered by the rapid onset of acquired resistance. Therefore, more drug discovery strategies are needed to promote the development of FGFR-targeted drugs. Here, we discovered compound S2h, a compound that selectively and effectively degrades FGFR1 at nanomolar concentrations in KG1a cells (IC 50  = 26.81 nM; DC 50  = 39.78 nM), which incorporates an essential, nine atom-long linkers. The importance of linker length, composition, and tethering site proteolysis-targeting chimeras (PROTACs) design is emphasized, and slight modifications can significantly affect degradation potency. Meanwhile, it was verified that the degradation of FGFR1 protein at compound S2h was concentration- and time-dependent and that the protein degradation occurred through the ubiquitin-proteasome system (UPS). In summary, the newly designed heterobifunctional FGFR1 degrader, compound S2h, provides new ideas and references for the research of FGFR small-molecule degraders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ruthenium complexes incorporating 2,2' : 6',2''-terpyridine ligands have emerged as promising candidates due to their versatile biological activities including DNA-binding, anti-inflammatory, antimicrobial, and anticancer properties. In this study, three new 4'-functionalized bis(terpyridine) Ru(II) complexes were synthesized. These complexes feature one ligand as 4-(2,2' : 6',2''-terpyridine-4'-yl) benzoic acid and the second ligand as either 4'-(2-thienyl)-2,2' : 6',2''-terpyridine, 4'-(3,4-dimethoxyphenyl)-2,2' : 6',2''-terpyridine, or 4'-(4-dimethylaminophenyl)-2,2' : 6',2''-terpyridine. Besides the chemical characterization by 1 H and 13 C NMR, mass spectrometry, and absorption and emission spectroscopy, the complexes were tested for their biological activity as anti-inflammatory, anticancer, and antimicrobial agents. Moreover, the toxicity of the Ru(II) complexes was assessed and benchmarked against diclofenac potassium and ibuprofen using a haemolysis assay. Biological evaluations demonstrate that these ruthenium complexes exhibit promising therapeutic potential with reduced haemolytic activity compared to standard drugs. They demonstrate substantial anti-inflammatory effects through inhibition of albumin denaturation along with moderate cytotoxicity against cancer cell lines and broad-spectrum antimicrobial activity. These findings highlight the multifaceted biomedical applications of 4'-functionalized bis(terpyridine) Ru(II) complexes, suggesting their potential for further development as effective and safe therapeutic agents., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

Promoting ferroptosis in tumor cells has emerged as a promising strategy for cancer therapy. Nonetheless, the heightened antioxidant activity within tumor cells hampers this approach, diminishing its effectiveness and fostering drug resistance. In this study, a new type of sulfasalazine (SAS) loaded nanoframe self-etched Pt-Co nanodendrites (Pt/Co-BNN@SAS) was developed, presenting a novel avenue for inducing ferroptosis in tumor cells by depleting glutathione (GSH) for cancer treatment. Pt/Co-BNN exhibits notable peroxidase (POD) activity, catalyzing the production of abundant oxygen radicals through the consumption of hydrogen peroxide (H 2 O 2 ) and the concurrent depletion of GSH. Simultaneously, the liberated sulfasalazine (SAS) from Pt/Co-BNN@SAS effectively obstructs system xc - , impeding the absorption of cystine by tumor cells and thereby expediting GSH depletion. The expeditious reduction of GSH markedly stimulates the accumulation of lipid peroxides (LPO) and suppresses glutathione peroxidase 4 (GPX4), consequently triggering ferroptosis in bladder cancer cells and inhibiting the migration ability of bladder cancer cells effectively. This research contributes to a more profound comprehension of nano-drug-biological interactions and provides a prospective outlook on treating bladder cancer by instigating ferroptosis in tumor cells through GSH depletion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024. Published by Elsevier B.V.)

For tumor treatment, the efficiency of single chemotherapeutic agent is generally limited and the traditional combination chemotherapies frequently result in the aggravation of side effects. Herein, an amphiphilic pillararene-based self-assembled nanoparticle (APSN) composed of hydrazide-pillar[5]arene (HP5A-6C) that achieve effective co-delivery of therapeutic combinations was reported. Through integrating multitudinous macrocyclic cavities into a single nanoparticle, the APSN could co-load two antitumor drugs, cisplatin (CP) and nitrogen mustard (NM) via host-guest interactions. A serious of safety tests preliminary demonstrated that blank carrier APSN had good biocompatibility. Cytotoxicity assay verified that co-delivery system CP+NM@APSN could exert a synergistic antitumor effect at the cellular level. In vivo studies demonstrated that CP+NM@APSN could not only improve chemotherapeutic outcomes in tumor-bearing model mouse but also alleviate two medications-related side effects. These favorable findings were attributed to the formation of ternary supramolecular assembly that benefited from an enhanced permeability and retention effect. © 2024 Elsevier Science. All rights reserved., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Deprivation of oxygen and scavenging of reactive oxygen species (ROS) severely restrict the antitumor efficiency of sonodynamic therapy (SDT). To address these challs, we report the Bi 2 MoO 6 /Prussian Blue-Au (BMO/PB-Au) nanosystem as piezoelectric sonosensitiser for highly efficient ROS production under ultrasonic irradiation. In this system, the nanosystem has catalase-like (CAT) and glutathione oxidase (GSHOD) catalytic activity, which can enhance SDT effectively by producing reactive oxygen species and consuming glutathione (GSH). While the narrow bandgap and heterojunctions contribute to the improved charge separation and charge recombination suppression of the piezoelectric semiconductor BMO, accelerating ROS generation. Packaging MCF-7 cancer cell membranes (CM) on the surface of BMO/PB-Au will effectively improve the enrichment of nanoparticles in tumor tissue. The in vivo results showed that the BMO/PB-Au@CM nanoplatform can effectively inhibit tumor growth through the enhanced SDT effect. Our findings provide a paradigm to rationally design hypoxia-relieve and GSH-depleted SDT platform to for promoting cancer therapy efficiency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Seven flavanones, including two new compounds coupled with styryl units, communins C ( 1 ) and D ( 2 ), as well as five known compounds, were isolated from Polytrichum commune Hedw. The planar structures of all compounds were determined using extensive spectroscopic analysis. The absolute configurations of two new compounds were assigned by comparing experimental ECD with calculated ECD. The cytotoxicity of all isolates against HCT-116, BGC803, MCF7 and PANC-1 cell lines was evaluated. Communin D exhibited significant cytotoxic activity on BGC803 cells with an IC 50 value of 9.3 μM.

The transforming growth factor β (TGF-β) type 1 receptor (ALK5) plays a key role in tumor microenvironment. Small-molecule inhibitors of TGFβR1 provides a prospective approach for the treatment of malignant tumors. In this study, a series of 4-((3-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)oxy)quinoline derivatives were identified as novel, potential TGFβR1 inhibitors. The most potent compound 16w inhibited SMAD2/3 phosphorylation and H22 cell viability with IC 50 values of 12 and 65 nM, respectively. Further, compound 16w exhibited reasonable pharmacokinetic profiles and exhibited significant anti-tumor efficacy in a xenograft model of H22 cells, with TGI of 79.6 %. Additionally, compound 16w also showed a strong synergistic proapoptotic effect in combination with sorafenib, which provided a promising lead for further development of novel anticancer drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

The biological activity of both cyclophosphazenes and peptides makes these compounds important for new studies in medicinal chemistry. For this purpose, five different phosphazene-peptide conjugates synthesized from dichlorocyclotriphosphazene and tyrosine-containing tripeptides. The synthesized compounds were evaluated for their in vitro cytotoxic activities against human breast (MCF-7) and colon (Caco-2) cancer cell lines using MTT assay. The derivatives induced cell death through DNA damage, with notable effects in Caco-2 cell lines. Specifically, DTVV, DTVG, and DTVA were cytotoxic at 50 and 100 μM, while DTVP and DTVM were effective at 25, 50, and 100 μM. DTVM outperformed Tamoxifen at 50 μM in the MCF-7 cell line. DNA damage studies of the compounds were performed using the comet assay method, evaluating tail length, tail density, olive tail moment, head length, and head density parameters. The findings indicated that cell death occurred via a DNA damage mechanism. The molecular intricacies of DTVA, DTVG, DTVM, DTVP and DTVV within the VEGFR2 kinase domain (3VHE) and Cyclophilin&#95;CeCYP16-Like Domain (2HQ6) binding pockets and various interactions, docking scores and potential activities of these derivatives were investigated. The differences in docking scores and interaction profiles highlight the potential efficacy and specificity of these compounds in targeting breast and colon cancer cells. These findings highlight the potential of phosphazene-peptide derivatives as therapeutic agents in cancer treatment., (© 2024 Wiley-VCH GmbH.)

New phthalazine-derived inhibitors for VEGFR-2 were synthesized for anticancer evaluations. Also, docking studies were performed to explore the suggested binding orientations of the novel derivatives inside the binding site of VEGFR-2. The achieved biological data were extremely interrelated to that of docking study. In specific, derivative 3f was the greatest effective compound against HepG2 and MCF-7 cancer cell lines with IC 50  = 0.17 ± 0.01 and 0.08 ± 0.01 µM individually. The six highly active derivatives 3b, 3e, 3f, 3g, 6a, and 6b were estimated for their VEGFR-2 inhibitory effects. Derivative 3f was the greatest effective compound which inhibited VEGFR-2 at IC 50  = 0.0557 ± 0.002 µM. The activities of 3f were assessed against MCF-7 cancer cells for apoptosis induction, cell cycle distribution, and growth inhibition. Compound 3f induced early apoptosis (21.44%) by more than 36 folds over the control (0.59%). The obtained results showed that compound 3f induced necrotic effect (6.03%) by more than threefolds over the control (1.75%). On the other hand, compound 3f improved the level of the pro-apoptotic protein; Bax by approximately fivefolds. Moreover, compound 3f noticeably decreased the levels of the anti-apoptotic proteins Bcl-2 by nearly fourfolds in comparison to the control. In addition, derivative 3f remarkably enhanced the Bax/Bcl2 ratio by nearly 18 folds, as compared to the control. Finally, our derivatives 3f, 3g, and 6b revealed good in silico considered ADMET profile in comparing to sorafenib., (© 2024 Wiley Periodicals LLC.)

Inhibitors of tubulin polymerization represent a promising therapeutic approach for the treatment of solid tumors. Molecules that bind to the colchicine site are of interest as they can function with a dual mechanism of action as both potent antiproliferative agents and tumor-selective vascular disrupting agents (VDAs). One such example is a 2-aryl-3-aroyl-indole molecule (OXi8006) from our laboratory that demonstrates potent inhibition of tubulin polymerization and strong antiproliferative activity (cytotoxicity) against a variety of human cancer cell lines. A water-soluble prodrug OXi8007, synthesized from OXi8006, demonstrates in vivo disruption of tumor-associated microvessels in several tumor types (mouse models). The molecular framework of OXi8006 inspired a series of fourteen new 2-aryl-3-aroyl-indole analogues that incorporated various functional group modifications on both the indole core and the aroyl ring. Electron withdrawing and donating groups at the mono-substituted 3' position and the di-substituted 3',5' positions were all accommodated while maintaining inhibition of tubulin polymerization (IC 50  < 5 μM), with several analogues demonstrating activity comparable to OXi8006 and the benchmark natural product combretastatin A-4 (CA4). Preliminary structure-activity relationship (SAR) studies were further enhanced by molecular docking to predict possible colchicine site interactions. Two analogues (KGP366 and KGP369) previously synthesized in our laboratory were re-synthesized using a somewhat modified route to increase synthetic efficiency and were subsequently converted to their corresponding water-soluble phosphate prodrug salts to evaluate their efficacy as VDAs. Administration of the prodrug salt (KGP415) of KGP369 caused significant reduction in bioluminescence signal from an orthotopic kidney tumor (RENCA-luc) in BALB/c mice, indicative of VDA activity. Collectively, these new functionalized indole-based analogues have extended SAR knowledge related to the colchicine binding site, and the most biologically active analogues hold promise for continued development as pre-clinical candidates for cancer therapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kevin G. Pinney reports financial support was provided by National Institutes of Health. Kevin G. Pinney reports financial support was provided by Cancer Prevention and Research Institute of Texas. Mary Lynn Trawick reports financial support was provided by National Institute of Health. Mary Lynn Trawick reports financial support was provided by Cancer Prevention and Research Institute of Texas. Ralph P. Mason reports financial support was provided by National Institutes of Health. Kevin G. Pinney has patent pending to Baylor University. Mary Lynn Trawick has patent pending to Baylor University. Zhe Shi has patent pending to Baylor University. Rebecca Vairin has patent pending to Baylor University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Conventional chemotherapy drugs are difficult to effectively target tumor tissue, leading to poor treatment outcomes and side effects. Actively targeted and stimuli-responsive nanomedicine greatly improves this situation, allowing for more precise drug accumulation at tumor sites. Herein, carboxymethyl-β-cyclodextrin (CMCD) - based host-guest nanocomposites (NPs) encapsulating hydroxycamptothecin (HCPT) were fabricated, which responded to esterase and had the function of targeting CD 44 receptors and the nucleus. PS-CMCD was firstly synthesized through an amide reaction of protamine (PS) and CMCD to enhance the function of penetrating membrane and nuclear localization. PS-CMCD/HCPT/HA NPs were then prepared by the host-guest complexation of PS-CMCD and HCPT and followed by surface modification of hyaluronic acid (HA) with CD44 receptor-targeting properties. The successful inclusion was also validated through computer simulation. The obtained nanocomposites displayed the esterase-responsive release behaviors of HCPT. Moreover, the synthesized PS-CMCD/HCPT/HA NPs enhanced the intracellular drug uptake due to the tumor cell- and nuclear-mediated targeting. In addition, in vivo application exhibited that PS-CMCD/HCPT/HA NPs realized good antitumor effects. These findings suggested its potential for targeted delivery and more effective tumor therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)