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The distinct conformational characteristics, functionality, affordability, low toxicity, and usefulness make calixarene-based compounds a promising treatment option for cancer. The aim of the present study is to synthesize a new calixarene-based compound and assess of its anticancer potential on some human cancer cells. The synthesized C-4-Hydroxyphenylcalix[4] resorcinarene (HPCR) was characterized by several spectroscopic techniques such as 1HNMR, 13CNMR, and X-ray crystallographic analysis to confirm its purity and identity. IC50 values were identified for cancer cell lines (U-87, MCF-7, A549) and human dermal fibroblasts cell line (HDF) after treatment with HPCR and the standard drug Cisplatin. A significant selective growth inhibitory activity against U-87 and A549 cell lines was obtained at an HPCR concentration of 100 μM. The MOE docking module (version 2015) was utilized to assess the extent of inhibition for HPCR compound against four cancer-related proteins (3RJ3, 7AXD, 6DUK, and 1CGL). [ABSTRACT FROM AUTHOR]

Abstract The distinct conformational characteristics, functionality, affordability, low toxicity, and usefulness make calixarene-based compounds a promising treatment option for cancer. The aim of the present study is to synthesize a new calixarene-based compound and assess of its anticancer potential on some human cancer cells. The synthesized C-4-Hydroxyphenylcalix[4] resorcinarene (HPCR) was characterized by several spectroscopic techniques such as 1HNMR, 13CNMR, and X-ray crystallographic analysis to confirm its purity and identity. IC 50 values were identified for cancer cell lines (U-87, MCF-7, A549) and human dermal fibroblasts cell line (HDF) after treatment with HPCR and the standard drug Cisplatin. A significant selective growth inhibitory activity against U-87 and A549 cell lines was obtained at an HPCR concentration of 100 μM. The MOE docking module (version 2015) was utilized to assess the extent of inhibition for HPCR compound against four cancer-related proteins (3RJ3, 7AXD, 6DUK, and 1CGL).

This research has developed an improved lyophilized formulation for Pemetrexed to enhance its stability using various techniques such as amino acids, boric acid, and sugars. The preliminary screening identified sorbitol as the most suitable sugar and L-Arginine as most suitable amino acid due to low degradation rate and minimal change in reconstitution time after one month of storage under accelerated stability conditions. 32 factorial design was employed to optimize the formulation, considering the drug-to-boric acid ratio (X1 factor) and the drug-to-L-Arginine ratio (X2 factor). The Design-Expert® software was utilized to generate optimized formula based on the results of nine batches. The desired responses included the % assay of the lyophilized and reconstituted formulations, reconstitution time, and pH of the composition. The optimized batch exhibited results in-line with the software predictions. Stability testing of the optimized batch under accelerated conditions (for six months revealed no significant differences in the evaluation parameters. Furthermore, the optimized formulation outperformed the marketed formulation. Cell line studies conducted on Pemetrexed API and the formulated dosage form demonstrated enhanced efficacy of the formulation, indicated by a lower IC50 value compared to Pemetrexed API alone. These comprehensive studies confirmed the stability of the prepared dosage form. [ABSTRACT FROM AUTHOR]

Blocked isocyanate-terminated polyurethane dendrimers of first-generation (G1) to third-generation (G3) build-up with bis-indolyl units were subjected to urethane interchange reaction with 4-hydroxy-2, 2, 6, 6-tetramethylpiperidin-1-yloxyl (4-hydroxy TEMPO). The resulting free radical functionalized dendrimers were thoroughly characterized. The electron paramagnetic resonance (EPR)and vibrating sample magnetometer (VSM) results confirmed that these radical dendrimers are stable and paramagnetic. The cytotoxic effect of G1–G3 TEMPO-dendrimers was studied comprehensively across various cancer cell lines, encompassing human breast cancer (MCF-7 and MDA-MB-231), cervical cancer (SiHa), and lung cancer (A549 and NCI-H460), as well as normal lung epithelial cells (L132). It was observed that these TEMPO-dendrimers exerted cytotoxic effects in all cancer cell lines while demonstrating minimal impact on lung epithelial cells. Notably, MDA-MB-231 displayed heightened susceptibility to the TEMPO-dendrimers. Cell cycle analysis and morphological studies revealed that the TEMPO-dendrimers induced G1 phase cell cycle arrest and cell death specifically in breast cancer cells. Further investigations unveiled that these TEMPO-dendrimers triggered oxidative stress-mediated cell death specifically in breast cancer cells. All these findings suggest that the TEMPO radical dendrimers reported in this work exhibited cytotoxic effects in cancer cells by stimulating oxidative stress. [ABSTRACT FROM AUTHOR]

Thyroid cancer (TC) and thyroid autoimmune disorders (AITD) are among the most common diseases in the general population, with higher incidence in women. Chronic inflammation and autoimmunity play a pivotal role in carcinogenesis. Some studies, indeed, have pointed out the presence of AITD as a risk factor for TC, although this issue remains controversial. Prevention of autoimmune disease and cancer is the ultimate goal for clinicians and scientists, but it is not always feasible. Thus, new treatments, that overcome the current barriers to prevention and treatment of TC and AITD are needed. Alkaloids are secondary plant metabolites endowed with several biological activities including anticancer and immunomodulatory properties. In this perspective, alkaloids may represent a promising source of prophylactic and therapeutic agents for TC and AITD. This review encompasses the current published literature on alkaloids effects on TC and AITD, with a specific focus on the pathways involved in TC and AITD development and progression. [ABSTRACT FROM AUTHOR]

A diverse array of aquatic ecosystems are inhabited by the euglenophytes, a group of autotrophic and eukaryotic organisms. In inland waterbodies, the red bloom is caused by a rapid development or accumulation of euglenophytes. Recent studies have designated euglenophytes as bioindicator of organic pollution. The ecology of euglenophytes is influenced by the changes in the intensity of sunlight, temperature, nutrient cycles, and seasons. Most of the species of euglenophytes grow prolifically with the increase of water temperature. Nitrogen and phosphorus are often thought to be the main nutrients that influence the cellular growth of toxic euglenophytes. A high concentration of nutrients is required for the euglenophytes to grow and to form bloom. Heavy bloom of euglenophytes in the summer season is the characteristic of eutrophic ponds. Inland waterbodies in many countries suffer from euglenophyte blooms, which shade submerged vegetation, deplete the dissolved oxygen and disrupt the aquatic food webs. Dense bloom of euglenophytes clog the gills of fishes, cause breathing difficulties and in extreme cases results mortality. Red blooms of the deadly toxin producing Euglena sanguinea negatively affect the water quality resulting massive mortality of fishes. Consequently, aquaculture systems and fisheries are facing a serious threat from the predicted outbreak of toxic red blooms of euglenophytes worldwide. To ensure sustainability in the fisheries and aquaculture industry, it is essential to analyze the ecology of euglenophytes. Again, interesting research on euglenophycin, a Euglena-derived natural product, has shown that it can be utilized as a potential anti-cancer drug. This paper comes up with a thorough review of the latest research in this area, revealing new insights and solutions that can help mitigate the negative impact of the freshwater harmful euglenophytes. By implementing considerable management strategies, the health of the valuable aquatic ecosystems and the future of the aquaculture and fisheries can also be secured.

Abstract Background Despite recent advances in the treatment of lung and breast cancer, the mortality with these two types of cancer is high. Xanthohumol (XN) is known as a bioactive compound that shows an anticancer effect on cancer cells. Here, we intended to investigate the anticancer effects of XN on the breast and lung cancer cell lines, using the three-dimensional (3D) cell culture. Methods XN was isolated from Humulus lupulus using Preparative-Thin Layer Chromatography (P-TLC) method and its authenticity was documented through Fourier Transform Infrared spectroscopy (FT-IR) and Hydrogen Nuclear Magnetic Resonance (H-NMR) methods. The spheroids of the breast (MCF-7) and lung (A549) cancer cell lines were prepared by the Hanging Drop (HD) method. Subsequently, the IC50s of XN were determined using the MTT assay in 2D and 3D cultures. Apoptosis was evaluated by Annexin V/PI flow cytometry and NFκB1/2, BAX, BCL2, and SURVIVIN expressions. Cell cycle progression was determined by P21, and P53 expressions as well as PI flow cytometry assays. Multidrug resistance was investigated through examining the expression of MDR1 and ABCG2. The invasion was examined by MMP2, MMP9, and FAK expression and F-actin labeling with Phalloidin-iFluor. Results While the IC50s for the XN treatment were 1.9 µM and 4.74 µM in 2D cultures, these values were 12.37 µM and 31.17 µM in 3D cultures of MCF-7 and A549 cells, respectively. XN induced apoptosis in MCF-7 and A549 cell lines. Furthermore, XN treatment reduced cell cycle progression, multidrug resistance, and invasion at the molecular and/or cellular levels. Conclusions According to our results of XN treatment in 3D conditions, this bioactive compound can be introduced as an adjuvant anti-cancer agent for breast and lung cancer.

Chemotherapy is an indispensable tool in medicine where small molecules act as potential cytotoxic, apoptotic, anti-angiogenic and anti-invasive agents targeting cancer cells. Chemotherapeutic agents possessing these multifaceted properties are highly warranted now as the mortality rate is increasing alarmingly. Tetrazole derivatives are well known for their pharmacological activity against various types of cancer progression. Herein, six derivatives of tetrazoles were synthesised by multicomponent reactions (MCR) and assessed their in vitro anticancer effects. The cytotoxic profiling of these compounds demonstrated that these compounds were active against a panel of breast cancer cells with highest anti-proliferative action against MCF-7. Among the six compounds, DTS 3 with a Chlorine atom demonstrated higher anti-proliferative and cytotoxic effects, which was selected for further investigations. Molecular docking and simulation analysis revealed preferential binding affinity of DTS 3 to CDK6;suggesting its likely role as CDK 6 inhibitor. Interestingly, the entire series of compounds were found to be more potent against cells expressing estrogen receptors, suggesting their dependence on ER signaling cascade. Further analysis revealed their potential to exert anti-invasive effects as well, among which DTS 3 possessed maximal anti-proliferative, anti-apoptotic, and anti-invasive properties suggesting its possible potential as a promising multi-faceted anti-cancer agent.

In this study, the fraction of the Hemiscorpius lepturus scorpion venom was subjected. The two bioactive fractions (F2 and F4) were separated and collected by RP-HPLC. Next, the cytotoxicity of F2 and F4 against human red blood cells and MCF-7 cell line was investigated. The expression levels of Bax, Bcl-2, and p53 genes in cancer cells treated with fractions were determined. In order to evaluate the effects of the two extract fractions, breast cancer was induced in BALB-c mice developed by the injection of MCF-7 cells. Following the intraperitoneal injection of F2 and F4 into mice, the levels of IFN-γ and IL-4 were measured using ELISA. The effects of fractions on the survival of MCF-7 cancer cells were significant compared to normal cells (p < 0.001), while they had no significant hemolysis activity against red blood cells (p > 0.05). The results showed that the expression of Bax and p53 was increased in MCF-7 cells treated with fractions compared to control cells without treatment, while the expression of Bcl-2 was decreased. The results of the in vivo analysis showed that the level of IFN-γ was increased, whereas the level of IL-4 was significantly reduced in mice treated with F2 and F4 at the concentrations of 5 and 10 mg/kg compared to control animals (p < 0.0001). Based on the results, two extract fractions of H. lepturus scorpion venom exert anti-cancer properties, and they are able to modulate the immune system and induce apoptosis in cancer cells. [ABSTRACT FROM AUTHOR]

Src homology 2 domain-containing phosphatase 2 (SHP2) is an attractive target for cancer therapy due to its multifaceted roles in both tumor and immune cells. Herein, we designed and synthesized a novel series of proteolysis targeting chimeras (PROTACs) using a SHP2 allosteric inhibitor as warhead, with the goal of achieving SHP2 degradation both inside the cell and in vivo. Among these molecules, compound P9 induces efficient degradation of SHP2 (DC50 = 35.2 ± 1.5 nM) in a concentration- and time-dependent manner. Mechanistic investigation illustrates that the P9-mediated SHP2 degradation requires the recruitment of the E3 ligase and is ubiquitination- and proteasome-dependent. P9 shows improved anti-tumor activity in a number of cancer cell lines over its parent allosteric inhibitor. Importantly, administration of P9 leads to a nearly complete tumor regression in a xenograft mouse model, as a result of robust SHP2 depletion and suppression of phospho-ERK1/2 in the tumor. Hence, P9 represents the first SHP2 PROTAC molecule with excellent in vivo efficacy. It is anticipated that P9 could serve not only as a new chemical tool to interrogate SHP2 biology but also as a starting point for the development of novel therapeutics targeting SHP2. [ABSTRACT FROM AUTHOR]

An efficient and greener approach for Knoevenagel condensation between substituted aldehydes and ketones with active methylene compound as starting substrate has been achieved using aqueous extract of Muca Acuminata as a neutral heterogeneous biocatalyst (Characterized by XRD, TEM, EDS, and ICP‐MS) at room temperature is reported. We found that this method is advantageous over the traditional methods that include refluxing, heating, use of toxic and highly expensive catalyst or solvents and also reduced the reaction time. It is ascertained that the reactions via this protocol are very clean and the isolated crude solid product is more than 95 % pure. The synthesized arylidene compounds exhibited great antioxidant potential and also acts as specific protein‐tyrosine kinase inhibitors and thus serves as an anticancer agent. The final product is separated by simple filtration and is characterized by various spectroscopic techniques like FT‐IR, 1H‐NMR, 13C‐NMR, 19F‐NMR and MS. The cheaper, simple and green approach suggests the possible use of this protocol for large scale preparations. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) continues to be devastating due to its highly malignant nature and poor prognosis. The limited benefits of the chemotherapeutic drugs and increasing resistance pose a critical challenge to overcome and warrant investigations for new therapeutic agents. Several preclinical and clinical studies have suggested a possible role of the androgen receptor (AR) signaling pathway in PC development and progression. Nevertheless, the studies are limited and inconclusive in explaining the molecular link between AR signaling and PC. Selective androgen receptor modulators (SARMs) are small molecule drugs with high affinity for the androgen receptor. SARMs elicit selective anabolic activities while abrogating undesired androgenic side effects. There is no study focusing on the utility of SARMs as inhibitors of PC. Here, we report the first study evaluating the possible anti-carcinogenic influences of andarine, a member of the SARMs, on PC. The data we presented here has illustrated that andarine repressed PC cell growth and proliferation via cell cycle arrest at G 0 /G 1 phase. Gene expression analysis revealed that it downregulates CDKN1A expression level accordingly. Furthermore, we established that the anti-carcinogenic activity of andarine is not mediated by the PI3K/AKT/mTOR signaling pathway, a crucial regulator of cell survival. Our findings suggest that andarine might be considered as a prospective drug for PC. [Display omitted] • Andarine is a potent and highly bio-available selective androgen receptor modulator. • Andarine's anti-cancer properties have not been investigated in pancreatic cancer. • Andarine restricted cell proliferation and caused cell-cycle arrest at G 0 /G 1. • The observed activity was independent of PI3K/AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Oral cancer is a malignant tumor that primarily affects areas such as the lips, tongue, buccal mucosa, salivary gland, and gingiva and has a very high malignancy. Piperlongumine (PL), isolated from long pepper (Piper longum L.), is a natural alkaloid with pharmacological effects, such as anti-inflammatory and anti-atherosclerotic effects. The effect and mechanism of PL in oral cancer cell lines has not been explored. Therefore, this study aimed to investigate the mechanism of anticancer effects of PL in the human oral cancer cell lines MC-3 and HSC-4 in vitro. This study demonstrated that PL inhibits cell proliferation by inducing apoptosis and autophagy in human oral cancer cell lines, which was confirmed by the levels of apoptosis- and autophagy-related proteins through Western blotting. Moreover, the pharmacological blockade of autophagy activation by hydroxychloroquine (HCQ), an autophagy inhibitor, significantly improved PL-induced apoptosis in MC-3 cells, suggesting a cytoprotective effect. In addition, activation of the mitogen-activated protein kinase (MAPK) signaling pathway contributed to PL-induced apoptosis. Collectively, the study suggested that combining an autophagy inhibitor with PL treatment can exert effective anticancer properties in oral cancer cells by inducing apoptosis and cytoprotective autophagy via the JNK-mediated MAPK pathway. [ABSTRACT FROM AUTHOR]

Background: Despite recent advances in the treatment of lung and breast cancer, the mortality with these two types of cancer is high. Xanthohumol (XN) is known as a bioactive compound that shows an anticancer effect on cancer cells. Here, we intended to investigate the anticancer effects of XN on the breast and lung cancer cell lines, using the three-dimensional (3D) cell culture. Methods: XN was isolated from Humulus lupulus using Preparative-Thin Layer Chromatography (P-TLC) method and its authenticity was documented through Fourier Transform Infrared spectroscopy (FT-IR) and Hydrogen Nuclear Magnetic Resonance (H-NMR) methods. The spheroids of the breast (MCF-7) and lung (A549) cancer cell lines were prepared by the Hanging Drop (HD) method. Subsequently, the IC50s of XN were determined using the MTT assay in 2D and 3D cultures. Apoptosis was evaluated by Annexin V/PI flow cytometry and NFκB1/2, BAX, BCL2, and SURVIVIN expressions. Cell cycle progression was determined by P21, and P53 expressions as well as PI flow cytometry assays. Multidrug resistance was investigated through examining the expression of MDR1 and ABCG2. The invasion was examined by MMP2, MMP9, and FAK expression and F-actin labeling with Phalloidin-iFluor. Results: While the IC50s for the XN treatment were 1.9 µM and 4.74 µM in 2D cultures, these values were 12.37 µM and 31.17 µM in 3D cultures of MCF-7 and A549 cells, respectively. XN induced apoptosis in MCF-7 and A549 cell lines. Furthermore, XN treatment reduced cell cycle progression, multidrug resistance, and invasion at the molecular and/or cellular levels. Conclusions: According to our results of XN treatment in 3D conditions, this bioactive compound can be introduced as an adjuvant anti-cancer agent for breast and lung cancer. [ABSTRACT FROM AUTHOR]

This study investigates the synthesis of a new compound, PYR26, and the multi-target mechanism of PYR26 inhibiting the proliferation of HepG2 human hepatocellular carcinoma cells. PYR26 significantly inhibits the growth of HepG2 cells (p < 0.0001) and this inhibition has a concentration effect. There was no significant change in ROS release from HepG2 cells after PYR26 treatment. The mRNA expressions of CDK4, c-Met and Bak genes in HepG2 cells were significantly inhibited (p < 0.05), while mRNA expression of pro-apoptotic factors such as caspase-3 and Cyt c was significantly increased (p < 0.01). The expression of PI3K, CDK4 and pERK proteins decreased. The expression level of caspase-3 protein was increased. PI3K is a kind of intracellular phosphatidylinositol kinase. PI3K signaling pathway is involved in signal transduction of a variety of growth factors, cytokines and extracellular matrix and plays an important role in preventing cell apoptosis, promoting cell survival and influencing cell glucose metabolism. CDK4 is a catalytic subunit of the protein kinase complex and is important for G1 phase progression of the cell cycle. PERK refers to phosphorylated activated ERK, which is translocated from cytoplasm to the nucleus after activation, and then participates in various biological reactions such as cell proliferation and differentiation, cell morphology maintenance, cytoskeleton construction, cell apoptosis and cell canceration. Compared with the model group and the positive control group, the tumor volume of the nude mice in the low-concentration PYR26 group, the medium-concentration group and the high-concentration group was smaller, and the organ volume was smaller than that in the model group and the positive control group. The tumor inhibition rates of low-concentration group PYR26, medium-concentration group and high-concentration group reached 50.46%, 80.66% and 74.59%, respectively. The results showed that PYR26 inhibited the proliferation of HepG2 cells and induced apoptosis of HepG2 cells by down-regulating c-Met, CDK4 and Bak, up-regulating the mRNA expression of caspase-3 and Cyt c genes, down-regulating PI3K, pERK and CDK4 proteins and up-regulating the protein level of caspase-3. In a certain range, with the increase in PYR26 concentration, the tumor growth was slower and the tumor volume was smaller. Preliminary results showed that PYR26 also had an inhibitory effect on the tumors of Hepa1-6 tumor-bearing mice. These results suggest that PYR26 has an inhibitory effect on the growth of liver cancer cells, therefore it has potential to be developed into a new anti-liver cancer drug. [ABSTRACT FROM AUTHOR]

Since the report of the antibiotic with anticancer properties, scientists have been focusing to isolate and characterize novel anti-microbial natural products possessing anticancer activities. The current study describes the production of seaweed-associated heterotrophic Bacillus altitudinis MTCC13046 with potential anticancer properties. The bacterium was screened for its capacity to diminish the cell proliferation of the human hepatocellular adenocarcinoma (HepG2) cell line, without upsetting the normal cells. The bacterial extract showed anticancer properties in a dose-reactive form against HepG2 (IC50, half maximal inhibitory concentration ~ 29.5 µg/ml) on tetrazolium bromide analysis with less significant cytotoxicity on common fibroblast (HDF) cells (IC50 ~ 77 µg/ml). The potential antioxidant ability of the organic extract of B. altitudinis MTCC13046 (IC90 133 µg/ml) could corroborate its capacity to attenuate the pathophysiology leading to carcinogenesis. The results of the apoptosis assay showed that the crude extracts of B. altitudinis maintained 68% viability in normal cells compared to 11% in the cancer cells (IC50 76.9 µg/ml). According to the findings, B. altitudinis MTCC13046 could be used to develop prospective anticancer agents. [ABSTRACT FROM AUTHOR]

Oncolytic viral gene therapy is a directed approach to target cancer cells without affecting healthy cells of the body. Canine parvovirus (CPV2) is an oncolytic virus that precisely targets and destroys neoplastic cells by causing DNA damage, mitochondrial damage, and apoptosis. Non-structural gene 1 (NS1) of CPV, concerned with viral DNA replication is a key mediator of cytotoxicity of CPV and can specifically cause tumor cell lysis. In the present study, by using the transcriptomics approach, we tried to identify molecular pathways and key genes involved in CPV2.NS1 mediated 4T1 mice mammary tumor cell death. We identified necroptosis and mitochondrial damage-mediated apoptosis as major cell death pathways leading to CPV2.NS1 transfected 4T1 cancer cell death. Various DEGs identified in our study play an important role in pathways like the PI3K/AKT pathway, diverse metabolic pathways, MAPK signaling pathway, and FGF signaling pathway, whichare mostly dysregulated in cancerous conditions. Histone variant H2A.X genes, Capn2, and Mapk10/JNK are predicted as key genes that play a role in causing endoplasmic reticulum stress and mitochondrial damage, thereby leading to necroptosis and apoptosis. This study is a preliminary work done to identify key genes and molecular pathways involved in CPV2.NS1 mediated 4T1 cancer cells death which need to be further validated to establish this viral gene as a potent oncolytic agent. [ABSTRACT FROM AUTHOR]

Src homology 2 domain-containing phosphatase 2 (SHP2) is an attractive target for cancer therapy due to its multifaceted roles in both tumor and immune cells. Herein, we designed and synthesized a novel series of proteolysis targeting chimeras (PROTACs) using a SHP2 allosteric inhibitor as warhead, with the goal of achieving SHP2 degradation both inside the cell and in vivo. Among these molecules, compound P9 induces efficient degradation of SHP2 (DC50 = 35.2 ± 1.5 nM) in a concentration- and time-dependent manner. Mechanistic investigation illustrates that the P9-mediated SHP2 degradation requires the recruitment of the E3 ligase and is ubiquitination- and proteasome-dependent. P9 shows improved anti-tumor activity in a number of cancer cell lines over its parent allosteric inhibitor. Importantly, administration of P9 leads to a nearly complete tumor regression in a xenograft mouse model, as a result of robust SHP2 depletion and suppression of phospho-ERK1/2 in the tumor. Hence, P9 represents the first SHP2 PROTAC molecule with excellent in vivo efficacy. It is anticipated that P9 could serve not only as a new chemical tool to interrogate SHP2 biology but also as a starting point for the development of novel therapeutics targeting SHP2.

Abstract Cisplatin is the primary anti-cancer agent for the treatment of most solid tumors. However, platinum-based anti-cancer chemotherapy produces severe side effects due to its poor specificity. There are a broad interest and literature base for a novel mechanism of action on platinum derivatives. Additionally, combining cisplatin with histone deacetylase inhibitors (HDACi) such as 4-hydroxybenzoic acid derivatives showed promising results in treating solid tumors. Here we aimed to conjugate 4-hydroxybenzoic acid with platinum to obtain a novel platinum derivative that can overcome cisplatin resistance. Cis-4-hydroxyphenylplatinum(II)diamine compound was synthesized under mild conditions and characterized. Cytotoxicity assay was performed on SKOV3-Luc and A549-Luc cells. Hemocompatibility and serum protein binding analysis were performed. Treatment potential was evaluated in xenograft tumor models. Biodistribution was tested on tumor-bearing mice via Pt analysis in organs with ICP-MS, ex vivo. In this study, cis-4-hydroxyphenylplatinum (II) diamine was synthesized with a yield of 62%. The MTT assay on A549-Luc and SKOV3-Luc cell lines resulted in IC50 values of 17.82 and 7.81 μM, respectively. While tumor growth was continued in the control group, the tumor volume decreased in the treatment group. All results point to the conclusion that the new compound has the potential to treat solid tumors.

Cancer is exerting an immense strain on the population and health systems all over the world. Green tea because of its higher simple catechin content (up to 30% on dry weight basis) is greatly popular as an anti-cancer agent which is found to reduce the risks of cancer as well as a range of other diseases. In addition, several in vitro and in vivo studies have shown that green tea possesses copious health benefits like anti-diabetic, anti-obese, anti-inflammatory, neuro-protective, cardio-protective, etc. This review highlights the anti-carcinogenic effects of green tea catechins integrating the recent information to gain a clear concept. Special emphasis was given to the effectiveness of green tea polyphenols (GTP) in the prevention of cancer. Overall, green tea has been found to be effective to reduce the risks of breast cancer, ovarian cancer, liver cancer, colorectal cancer, skin cancer, prostate cancer, oral cancer, etc. However, sufficient information was not found to support that green tea consumption reduces the risk of lung cancer, esophageal cancer, or stomach cancer. The exciting data integrated into this article will increase interest in future researchers to garner more fruitful information on the relevant topics. [ABSTRACT FROM AUTHOR]

L‐type amino acid transporter 1 (LAT1; SLC7A5), which preferentially transports large neutral amino acids, is highly upregulated in various cancers. LAT1 supplies cancer cells with amino acids as substrates for enhanced biosynthetic and bioenergetic reactions and stimulates signalling networks involved in the regulation of survival, growth and proliferation. LAT1 inhibitors show anti‐cancer effects and a representative compound, JPH203, is under clinical evaluation. However, pharmacological impacts of LAT1 inhibition on the cellular amino acid transport and the translational activity in cancer cells that are conceptually pivotal for its anti‐proliferative effect have not been elucidated yet. Here, we demonstrated that JPH203 drastically inhibits the transport of all the large neutral amino acids in pancreatic ductal adenocarcinoma cells. The inhibitory effects of JPH203 were observed even in competition with high concentrations of amino acids in a cell culture medium. The analyses of the nutrient‐sensing mTORC1 and GAAC pathways and the protein synthesis activity revealed that JPH203 downregulates the global translation. This study demonstrates a predominant contribution of LAT1 to the transport of large neutral amino acids in cancer cells and the suppression of protein synthesis by JPH203 supposed to underly its broad anti‐proliferative effects across various types of cancer cells. [ABSTRACT FROM AUTHOR]

Oral cancer is a malignant tumor that primarily affects areas such as the lips, tongue, buccal mucosa, salivary gland, and gingiva and has a very high malignancy. Piperlongumine (PL), isolated from long pepper (Piper longum L.), is a natural alkaloid with pharmacological effects, such as anti-inflammatory and anti-atherosclerotic effects. The effect and mechanism of PL in oral cancer cell lines has not been explored. Therefore, this study aimed to investigate the mechanism of anticancer effects of PL in the human oral cancer cell lines MC-3 and HSC-4 in vitro. This study demonstrated that PL inhibits cell proliferation by inducing apoptosis and autophagy in human oral cancer cell lines, which was confirmed by the levels of apoptosis- and autophagy-related proteins through Western blotting. Moreover, the pharmacological blockade of autophagy activation by hydroxychloroquine (HCQ), an autophagy inhibitor, significantly improved PL-induced apoptosis in MC-3 cells, suggesting a cytoprotective effect. In addition, activation of the mitogen-activated protein kinase (MAPK) signaling pathway contributed to PL-induced apoptosis. Collectively, the study suggested that combining an autophagy inhibitor with PL treatment can exert effective anticancer properties in oral cancer cells by inducing apoptosis and cytoprotective autophagy via the JNK-mediated MAPK pathway.

Self‐assembly of (((1‐(pyridin‐2‐yl)ethylidene)hydrazono)methyl)phenol ligand (L1) and MnCl2 proceeded with the hydrolysis of the ligand affording the new [Mn(L2)Cl2]n 1D coordination polymer where L2 is 2‐(1‐hydrazonoethyl)pyridine. The structure of [Mn(L2)Cl2]n was confirmed using FTIR, CHN, and X‐ray diffraction of single crystal. It crystallized in the triclinic P‐1 crystal system with a = 7.0697(9) Å, b = 8.878(1) Å, c = 9.402(2) Å, α = 113.99(2)°, β = 95.48(1)°, γ = 111.77(1)°, and V = 479.13(15) Å3. The Mn(II) is octahedrally coordinated with two nitrogen atoms from L2 and four chloride ions. The chloride anions act as bridging ligand that connect the Mn(II) centers leading to the formation of the 1D polymer. Based on continuous shape (CShM) measure tool, the coordination configuration is closer to the octahedron rather than a trigonal prism. Using Hirshfeld analysis, the Cl ... H (29.2%), H ... C (13.6%), and C ... C (3.7%) contacts are the most important in the molecular packing of [Mn(L2)Cl2]n complex. The ligand L2 has better antibacterial, antifungal, and antioxidant activities than the Mn(II) complex. The [Mn(L2)Cl2]n complex has higher cytotoxic effect than L2 against both lung carcinoma A‐549 and lung fibroblast MRC‐5 cell lines. The IC50 and CC50 values of the Mn(II) complex are 26.09 ± 1.76 and 60.40 ± 3.74 μg ml−1, respectively, while 121.23 ± 5.91 and 241.13 ± 13.29 μg ml−1, respectively, for L2. [ABSTRACT FROM AUTHOR]

Simple Summary: The relationship between inflammation and carcinogenesis, as well as the response to anti-tumor therapy, is intimate. Atrial natriuretic peptides (ANPs) play a pivotal role in the homeostatic control of blood pressure, electrolytes, and water balance. In addition, ANPs exert immune-modulatory effects in the tissue microenvironment, thus exhibiting a fascinating ability to prevent inflammation-related tumorigenesis and cancer recurrence. In cancers, ANPs show anti-proliferative effects through several molecular pathways. Furthermore, ANPs attenuate the side effects of cancer therapy. Therefore, ANPs have potential therapeutic value in tumors. Here, we summarized the roles of ANPs in diverse aspects of the immune system and the molecular mechanisms underlying the anti-cancer effects of ANPs, contributing to the development of ANP-based anti-cancer agents. The atrial natriuretic peptide (ANP), a cardiovascular hormone, plays a pivotal role in the homeostatic control of blood pressure, electrolytes, and water balance and is approved to treat congestive heart failure. In addition, there is a growing realization that ANPs might be related to immune response and tumor growth. The anti-inflammatory and immune-modulatory effects of ANPs in the tissue microenvironment are mediated through autocrine or paracrine mechanisms, which further suppress tumorigenesis. In cancers, ANPs show anti-proliferative effects through several molecular pathways. Furthermore, ANPs attenuate the side effects of cancer therapy. Therefore, ANPs act on several hallmarks of cancer, such as inflammation, angiogenesis, sustained tumor growth, and metastasis. In this review, we summarized the contributions of ANPs in diverse aspects of the immune system and the molecular mechanisms underlying the anti-cancer effects of ANPs. [ABSTRACT FROM AUTHOR]

Various preclinical and clinical studies exhibited the potential of cannabis against various diseases, including cancer and related pain. Subsequently, many efforts have been made to establish and develop cannabis-related products and make them available as prescription products. Moreover, FDA has already approved some cannabis-related products, and more advancement in this aspect is still going on. However, the approved product of cannabis is in oral dosage form, which exerts various limitations to achieve maximum therapeutic effects. A considerable translation is on a hike to improve bioavailability, and ultimately, the therapeutic efficacy of cannabis by the employment of nanotechnology. Besides the well-known psychotropic effects of cannabis upon the use at high doses, literature has also shown the importance of cannabis and its constituents in minimising the lethality of cancer in the preclinical models. This review discusses the history of cannabis, its legal aspect, safety profile, the mechanism by which cannabis combats with cancer, and the advancement of clinical therapy by exploiting nanotechnology. A brief discussion related to the role of cannabinoid in various cancers has also been incorporated. Lastly, the information regarding completed and ongoing trials have also been elaborated. [ABSTRACT FROM AUTHOR]

Heat shock protein 27 (HSP27) is a protein that works as a chaperone and an antioxidant and is activated by heat shock, environmental stress, and pathophysiological stress. However, HSP27 dysregulation is a characteristic of many human cancers. HSP27 suppresses apoptosis and cytoskeletal reorganization. As a result, it is recognized as a critical therapeutic target for effective cancer therapy. Despite the effectiveness of multiple HSP27 inhibitors in pre-clinical investigations and clinical trials, no HSP27 inhibitor has progressed to the anticancer phase of the development. These difficulties have mostly been attributable to existing anticancer therapies' inability to target oncogenic HSP27. Highly selective HSP27 inhibitors with higher effective-ness and low toxicity led to the development of combination techniques that include computer-aided assisted therapeutic discovery and design. This study emphasizes the most recent results and roles of HSP27 in cancer and the potential for utilizing an anticancer chemical database to uncover novel compounds to inhibit HSP27. [ABSTRACT FROM AUTHOR]

In this study, a series of 14 Cu (II), Zn (II), Ni (II) and Ag (I) complexes containing bis-benzimidazole derivatives were successfully designed and synthesized from 2-(1H-benzimidazole-2-yl)-phenol derivatives and corresponding metal salt solutions. The compound structures were identified by FT-IR, 1H-NMR, powder X-ray diffraction and ESI-MS analyses, and the presence of the metal in the complexes was confirmed by ultraviolet-visible spectroscopy and ICP optical emission spectrometry. Electronic structure calculations were also carried out to describe the detailed structures in addition to the electronic absorption spectra of the ligands. The cytotoxic activity of the complexes was evaluated against three human cancer cell lines: lung (A549), breast (MDA-MB-231) and prostate (PC3) cancer cells. All complexes inhibited anti-proliferative cancer cells better than free ligands, especially Zn (II) and Ag (I) complexes, which are most sensitive to MDA-MB-231 cells. In addition, showing the growth inhibition of three cancer cell lines with IC50 < 10.4 µM, complexes C1, C3 and C14 could be considered potential multi-targeted anti-cancer agents.

The repurposing strategy of converting nimesulide from an anti-fever drug to an anti-cancer agent by modifying its main structure targeting HSP27 is gaining great attention these days. The goal of this study focuses on synthesizing a new nimesulide derivative with new ligands that have biological anti-cancer activities in different cancer models using the in-vitro assay. Nimesulide derivative L1 was synthesized, characterized by 1H NMR, 13C NMR, FTIR, melting point, mass spectra, and TGA analysis. A single crystal was diffracted and showed colorless block group P-1. The results revealed that L1 demonstrates potent anti-cancer activity with lung (H292), ovarian (SKOV3), and breast (SKBR3) cancer cell lines in-vitro models with IC 50 values below 8.8 µM. [ABSTRACT FROM AUTHOR]

Drug resistance, undesirable toxicity and lack of selectivity are the major challenges of conventional cancer therapies, which cause poor clinical outcomes and high mortality in many cancer patients. Development of alternative cancer therapeutics are highly required for the patients who are resistant to the conventional cancer therapies, including radiotherapy and chemotherapy. The success of a new cancer therapy depends on its high specificity to cancer cells and low toxicity to normal cells. Utilization of bacteria has emerged as a promising strategy for cancer treatment. Attenuated or genetically modified bacteria were used to inhibit tumor growth, modulate host immunity, or deliver anti-tumor agents. The bacteria-derived immunotoxins were capable of destructing tumors with high specificity. These bacteria-based strategies for cancer treatment have shown potent anti-tumor effects both in vivo and in vitro , and some of them have proceeded to clinical trials. Pseudomonas aeruginosa , a Gram-negative bacterial pathogen, is one of the common bacteria used in development of bacteria-based cancer therapy, particularly known for the Pseudomonas exotoxin A-based immunotoxins, which have shown remarkable anti-tumor efficacy and specificity. This review concisely summarizes the current knowledge regarding the utilization of P. aeruginosa in cancer treatment, and discusses the challenges and future perspectives of the P. aeruginosa -based therapeutic strategies. [ABSTRACT FROM AUTHOR]

Androgen receptor (AR)-castrate-resistant prostate cancer (CRPC) is an aggressive form of prostate cancer that does not have clinically approved targeted treatment options. To this end, the cytotoxic potential of raloxifene and the synthetic curcumin derivative 2,6-bis (pyridin-4-ylmethylene)-cyclohexanone (RL91) was examined in AR-(PC3 and DU145) cells and AR+ (LnCaP) CRPC cells. The results showed that both raloxifene and RL91 elicited significant cytotoxicity across three cell lines with the lowest EC50 values in PC3 cells. Additionally, the two drugs were synergistically cytotoxic toward the PC3, DU-145 and LNCaP cell lines. To determine the effect of the drug combination in vivo, an orthotopic model of CRPC was used. Male mice were injected with PC3 prostate cancer cells and then treated with vehicle (5 mL/kg), raloxifene (8.5 mg/kg, po), RL91 (8.5 mg/kg, po) or a combination of raloxifene and RL91 for six weeks. Sham animals were subjected to the surgical procedure but were not implanted with PC3 cells. The results showed that raloxifene decreased tumor size and weight as well as metastasis to renal lymph nodes. However, combination treatment reversed the efficacy of raloxifene as tumor volume and metastasis returned to control levels. The results suggest that raloxifene has tumor suppressive and anti-metastatic effects and has potential for further clinical use in AR-CRPC. [ABSTRACT FROM AUTHOR]

Drug resistance, undesirable toxicity and lack of selectivity are the major challenges of conventional cancer therapies, which cause poor clinical outcomes and high mortality in many cancer patients. Development of alternative cancer therapeutics are highly required for the patients who are resistant to the conventional cancer therapies, including radiotherapy and chemotherapy. The success of a new cancer therapy depends on its high specificity to cancer cells and low toxicity to normal cells. Utilization of bacteria has emerged as a promising strategy for cancer treatment. Attenuated or genetically modified bacteria were used to inhibit tumor growth, modulate host immunity, or deliver anti-tumor agents. The bacteria-derived immunotoxins were capable of destructing tumors with high specificity. These bacteria-based strategies for cancer treatment have shown potent anti-tumor effects both in vivo and in vitro, and some of them have proceeded to clinical trials. Pseudomonas aeruginosa, a Gram-negative bacterial pathogen, is one of the common bacteria used in development of bacteria-based cancer therapy, particularly known for the Pseudomonas exotoxin A-based immunotoxins, which have shown remarkable anti-tumor efficacy and specificity. This review concisely summarizes the current knowledge regarding the utilization of P. aeruginosa in cancer treatment, and discusses the challenges and future perspectives of the P. aeruginosa-based therapeutic strategies.

Carbonic anhydrase IX (CAIX) is a hypoxia-associated transmembrane protein that is critical in the survival of cells. Because CAIX has a key role in pH regulation, its therapeutic effects have been heavily studied by different research laboratories. This study aims to investigate how a synthetic CAIX inhibitor triggers apoptosis in a cancer cell line, HeLa. In this regard, we investigated the effects of the compound I , synthesized as a CAIX inhibitor, on the survival of cancer cells. The compound I inhibited the proliferation of the CAIX+ HeLa cells, kept the cells in G0/G1 phase (74.7%) and altered the cells morphologies (AO/EtBr staining) and the nuclear structure (γ-H2AX staining). CAIX inhibition triggered apoptosis in HeLa cells with a rate of 47.4%. According to the expression of mediator genes (CASP-3, -8, -9, BAX, BCL-2, BECLIN, LC3), the both death pathways were activated in HeLa cells with the inhibition of CAIX with the compound I. The compound I was also determined to affect the genes and proteins that have a critical role in the regulation of apoptotic pathways (pro casp-3, cleaved casp-3, -8, -9, cleaved PARP and CAIX). Furthermore, CAIX inhibition caused changes in pH balance, disruption in organelle integrity of mitochondria, and increase intracellular reactive oxygen level of HeLa cells. Taken together, our findings suggest that CAIX inhibition has a potential in cancer treatment, and the compound I , a CAIX inhibitor, could be a promising therapeutic strategy in the treatment of aggressive tumours. [ABSTRACT FROM AUTHOR]

The geometry of the title molecule [systematic name: 2-(2-nitrophenyl)-4H-chromen-4-one], C15H9NO4, is determined by two dihedral angles formed by the mean plane of phenyl ring with the mean planes of chromone moiety and nitro group, being 50.73 (5) and 30.89 (7)°, respectively. The crystal packing is determined by π–π interactions and C—H...O contacts. The results of DFT calculations at the B3LYP/6–31G* level of theory provided an explanation of the unusually large dihedral angle between the chromone moiety and the phenyl group. The electrostatic potential map on the molecular surface was calculated in order to determine the potential binding sites to receptors.

In this study, Co0.5Ni0.5Nd0.02Fe1.98O4 nanoparticles CoNiNd (NPs) were synthesized by combustion method linked with biosynthesis with and without different plant extracts such as Lavender, Ginger, Flax-Seed, Lemon Juice, Tragacanth Gum, and Dates Fruit. Co0.5Ni0.5Nd0.02Fe1.98O4 nanoparticles (NPs) with plant extracts (CoNiNd plant extracts) were analyzed by XRD, TEM and SEM methods. The structure of Co-Ni spinel ferrite was confirmed by XRD and the shape and the size of nanoparticles were examined via SEM and TEM and the size was found between 17 and 25 nm. The anti-cancer activity of NPs on cancer cells such as human colorectal carcinoma (HCT-116) and human cervical cells (Hela) were investigated. The cytotoxicity of was examined by MTT assay and followed by measuring the inhibitory concentration (IC50) values after 48 h treatments. The cell viability assay confirmed a decrease in the cancer cell viability post NPs treatments and showed dose-dependent inhibitory action. The treatments of CoNiNd (NPs) and CoNiNd plant extracts via Lavender plant extract showed most profound inhibitory action on both cancer cells than extracts other plant extracts. The IC50 values were for HCT-116 cells were found to be in range of 15.75–42.55 µg/mL and 13.44 to 35.65 µg/mL for HeLa cells. In contrast, the treatment of CoNiNd (NPs) and CoNiNd plant extracts showed inhibitory action but the percentage of inhibition was higher in HEK-293 cells. Our results showed that CoNiNd (NPs) and CoNiNd plant extracts possess potential application in the colon and cervical cancer treatments and we recommend molecular analysis of NPs mediated cancer cell death for future applications.

A stereoselective synthesis of a bioactive triarylmethane is described. Key to the synthesis is a nickel-catalyzed Suzuki-Miyaura coupling which proceeds with retention at the benzylic center. This method is complementary to our previously reported nickel-catalyzed Kumada coupling which proceeds with inversion. Together, the two methods allow for efficient access to either enantiomer of biologically relevant triarylmethanes from a common enantioenriched intermediate.

Cancer is exerting an immense strain on the population and health systems all over the world. Green tea because of its higher simple catechin content (up to 30% on dry weight basis) is greatly popular as an anti-cancer agent which is found to reduce the risks of cancer as well as a range of other diseases. In addition, several in vitro and in vivo studies have shown that green tea possesses copious health benefits like anti-diabetic, anti-obese, anti-inflammatory, neuro-protective, cardio-protective, etc. This review highlights the anti-carcinogenic effects of green tea catechins integrating the recent information to gain a clear concept. Special emphasis was given to the effectiveness of green tea polyphenols (GTP) in the prevention of cancer. Overall, green tea has been found to be effective to reduce the risks of breast cancer, ovarian cancer, liver cancer, colorectal cancer, skin cancer, prostate cancer, oral cancer, etc. However, sufficient information was not found to support that green tea consumption reduces the risk of lung cancer, esophageal cancer, or stomach cancer. The exciting data integrated into this article will increase interest in future researchers to garner more fruitful information on the relevant topics.

Despite the promising anti-cancer properties of the polyoxometalates (POMs) compound, they have not yet been reported for clinical use due to their general toxicity. This study reports the synthesis of tocopherol succinate (TS)-polyoxomolybdate (POMo) conjugate (T2POMo) as a novel organic–inorganic hybrid conjugate of POMo and evaluating its anti-cancer properties in vitro. The aim was to introduce a more potent derivative with less general toxicity than initial POMo to cancer treatment studies. The T2POMo conjugate was synthesized using amide bond formation between POMo and TS based on the carbodiimide strategy. The chemical structure of T2POMo conjugate was fully investigated and confirmed using spectroscopy and elemental analysis techniques. The anti-cancer properties of T2POMo conjugate were evaluated on Brest (MCF-7) and prostate cancer (LNCAP) cell lines carefully by the MTT protocol, and the general toxicity was studied on human umbilical vein endothelial cells (HUVEC) similarly. Finally, the quantity of induced apoptosis was carefully evaluated using the flow cytometry technique for the T2POMo conjugate compared to POMo. The cytotoxicity studies showed that tocopherol succinate conjugation altered and regulated the activity and seems to induce great synergistic cytotoxic effects on cancerous cell lines. The half-maximal inhibitory concentration (IC50) on the MCF-7 cell line was about 167.3 μg/mL, and on the LNCAP cell line was about 234.1 μg/mL. The cytotoxicity of T2POMo was significantly greater than that of POMo, and the toxic effects on normal cells were significantly reduced. Flow cytometry results showed that the hybrid conjugate could produce about 61% of apoptosis in the MCF-7 cell line than POMo (36%) alone. Therefore, tocopherol succinate hybrid conjugate (T2POMo) can be introduced as a promising potent anti-cancer agent to further pre-clinical studies. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of novel 2,3-di- O - and 3- O -sulfonate derivatives of 5,6- O -isopropylidene- l -ascorbic acid were synthesized, characterized, and evaluated for their anticancer activity. • Compounds 2b and 2c exhibited potent anticancer activity against MCF-7 (IC 50 = 0.04 μM and 0.81 μM, respectively) and A-549 (IC 50 = 0.1 μM and 0.9 μM, respectively) cancer cell lines. Notably, compound 2b displayed 89-fold selectivity for MCF-7 breast cancer over MCF-10A normal breast cells. • Compounds 2b and 2c exhibited remarkable inhibition of tubulin polymerization, with 73.12 % and 62.09 % inhibition, respectively, against A-549 lung cancer cells. • Molecular docking results revealed that all compounds were bound into the hydrophobic pocket of tubulin consisting of amino acid residues, and the interactions, pocket fit, and binding affinity resulted in higher docking scores compared to Colchicine. • In-silico ADMET predictions indicated favorable drug-like properties, with 2b exhibiting the highest binding affinity. A series of novel l -ascorbic acid derivatives bearing aryl and alkyl sulfonate substituents were synthesized and characterized. In vitro anticancer evaluation against MCF-7 (breast) and A-549 (lung) cancer cell lines revealed potent activity for most of the compounds, with 2b being equipotent to the standard drug colchicine against MCF-7 (IC 50 = 0.04 μM). Notably, compound 2b displayed 89-fold selectivity for MCF-7 breast cancer over MCF-10A normal breast cells. Derivatives with two sulfonate groups (2a-g, 3a-g) exhibited superior potency over those with one sulfonate (4a-c, 5g , 6b). Compounds 2b and 2c potently inhibited tubulin polymerization in A-549 cancer cells (73.12 % and 62.09 % inhibition, respectively), substantiating their anticancer potential through microtubule disruption. Molecular docking studies showed higher binding scores and affinities for these compounds at the colchicine-binding site of α, β-tubulin compared to colchicine itself. In-silico ADMET predictions indicated favourable drug-like properties, with 2b exhibiting the highest binding affinity. These sulfonate derivatives of l -ascorbic acid represents promising lead scaffolds for anticancer drug development. [ABSTRACT FROM AUTHOR]

This comprehensive review delves into the intricate world of the Quinoline scaffold, unravelling its pivotal role as a molecular cornerstone in the relentless battle against cancer, poised to emerge as an indispensable pharmacophore in the forefront of cutting-edge drug development. [Display omitted] • Mechanisms of Quinoline Anticancer Action. • Therapeutic Promise & Implications. • Quinoline-Based Compounds Review. This article includes a thorough examination of the inhibitory potential of quinoline-based drugs on cancer cells, as well as an explanation of their modes of action. Quinoline derivatives, due to their various chemical structures and biological activity, have emerged as interesting candidates in the search for new anticancer drugs. The review paper delves into the numerous effects of quinoline-based chemicals in cancer progression, including apoptosis induction, cell cycle modification, and interference with tumor-growth signaling pathways. Mechanistic insights on quinoline derivative interactions with biological targets enlightens their therapeutic potential. However, obstacles such as poor bioavailability, possible off-target effects, and resistance mechanisms make it difficult to get these molecules from benchside to bedside. Addressing these difficulties might be critical for realizing the full therapeutic potential of quinoline-based drugs in cancer treatment. [ABSTRACT FROM AUTHOR]

Heat shock protein 27 (HSP27) is a protein that works as a chaperone and an antioxidant and is activated by heat shock, environmental stress, and pathophysiological stress. However, HSP27 dysregulation is a characteristic of many human cancers. HSP27 suppresses apoptosis and cytoskeletal reorganization. As a result, it is recognized as a critical therapeutic target for effective cancer therapy. Despite the effectiveness of multiple HSP27 inhibitors in pre-clinical investigations and clinical trials, no HSP27 inhibitor has progressed to the anticancer phase of the development. These difficulties have mostly been attributable to existing anticancer therapies’ inability to target oncogenic HSP27. Highly selective HSP27 inhibitors with higher effective-ness and low toxicity led to the development of combination techniques that include computer-aided assisted therapeutic discovery and design. This study emphasizes the most recent results and roles of HSP27 in cancer and the potential for utilizing an anticancer chemical database to uncover novel compounds to inhibit HSP27.

The exploration into the strategies for the prevention and treatment of cancer is far from complete. Apart from humans, cancer has gained considerable importance in animals because of increased awareness towards animal health and welfare. Current cancer treatment regimens are less specific towards tumor cells and end up harming normal healthy cells. Thus, a highly specific therapeutic strategy with minimal side effects is the need of the hour. Oncolytic viral gene therapy is one such specific approach to target cancer cells without affecting the normal cells of the body. Canine parvovirus (CPV) is an oncolytic virus that specifically targets and kills cancer cells by causing DNA damage, caspase activation, and mitochondrial damage. Non-structural gene 1 (NS1) of CPV, involved in viral DNA replication is a key mediator of cytotoxicity of CPV and can selectively cause tumor cell lysis. In this review, we discuss the oncolytic properties of Canine Parvovirus (CPV or CPV2), the structure of the NS1 protein, the mechanism of oncolytic action as well as role in inducing an antitumor immune response in different tumor models.

The exploration into the strategies for the prevention and treatment of cancer is far from complete. Apart from humans, cancer has gained considerable importance in animals because of increased awareness towards animal health and welfare. Current cancer treatment regimens are less specific towards tumor cells and end up harming normal healthy cells. Thus, a highly specific therapeutic strategy with minimal side effects is the need of the hour. Oncolytic viral gene therapy is one such specific approach to target cancer cells without affecting the normal cells of the body. Canine parvovirus (CPV) is an oncolytic virus that specifically targets and kills cancer cells by causing DNA damage, caspase activation, and mitochondrial damage. Non-structural gene 1 (NS1) of CPV, involved in viral DNA replication is a key mediator of cytotoxicity of CPV and can selectively cause tumor cell lysis. In this review, we discuss the oncolytic properties of Canine Parvovirus (CPV or CPV2), the structure of the NS1 protein, the mechanism of oncolytic action as well as role in inducing an antitumor immune response in different tumor models. [ABSTRACT FROM AUTHOR]

• Phyllanthus emblica is an important medicinal plant with many benefits. • P. emblica L. holds a unique position in the Indian (Ayurvedic), Turkish, Unani, and Tibetan medicinal systems. • Therapeutic and healing potentials have made it a valid research option for the development of novel drug formulations with very low side effects. • This review article summarizes recent literature relevant to the nutritional, health, and therapeutic benefits of P. emblica Medicinal plants are precious gifts of nature, which may serve as a source of food and medicine to humans. Phyllanthus emblica L has held a unique position in the Indian (Ayurvedic), Turkish, Unani, and Tibetan medicinal systems for centuries. Its nutritional, therapeutic and healing potentials have made it a valid research option for the development of novel drug formulations with few side effects. The presence of vitamin C, alkaloids, ellagitannins, gallic acid, emblicanin A and emblicanin B, flavonoids (especially rutin and quercetin), and a variety of biological molecules, makes P. emblica, a valued medicinal plant. This review article summarizes the recent literature relevant to the nutritional, health, and therapeutic benefits of P. emblica, such as potential chemo-preventive, anti-diabetic, anti-microbial, anti-inflammatory, analgesic, anti-mutagenic, antioxidant, diuretic, aphrodisiac, UV protectant, and anti-aging activities. Its applications in memory enhancing, respiratory, skin and ophthalmic disorders, and detoxification including that of snake venom, are also highlighted. It additionally reviews retrospective studies on P. emblica at the molecular level, for disease management and control. P. emblica is an important medicinal plant with many benefits. It has been used for centuries and generations as a source of food because of its unique restorative and rejuvenating potential. Thus, in light of the sum of these investigations, new studies could be designed to explore valuable bioactive compounds present throughout in nature in the form of plants [ABSTRACT FROM AUTHOR]

Two new mono‐ and dinuclear zinc (II) complexes with a formula of [Zn (LN)OMeCl] (1) and [Zn2(LN)(N3)2Cl2] (2) [where LN = 1,1,3,3‐tetrakis(3,5‐dimethyl‐1‐pyrazolyl)propane)] have been synthesized in methanol as a solvent and fully characterized by the single crystal X‐ray diffraction, elemental analysis, FT‐IR, UV–Vis, density functional theory (DFT) calculations, antibacterial, and anticancer properties. In both of them, zinc ion is tetrahedrally coordinated to two nitrogen atoms from one of the chelating bidentate bis(3,5‐dimethylpyrazolyl)methane units of the LN ligand and one terminal chlorine. The forth coordination site was occupied by methoxy group in 1 and azide co‐ligand in complex 2. In contrast to 1, in the structure of 2 two metal centers are bridged by the tetradentate chelating LN ligand to form a dinuclear complex. Interestingly, the environment around the central atom in these complexes are mimicked with the core structure of the zinc metalloproteinases, Thermolysin {[NNO]ZnX} and Carbonic anhydrase {[NNN]ZnX} for complexes 1 and 2, respectively. Data analysis of the antibacterial activities demonstrated that the gram positive species showed more sensitivity toward the target title agents. Although, both complexes exhibit antibacterial activities and kill bacteria at low concentration, but complex 1 has higher DNA cleavage activity than 2. Additionally, the cytotoxicity of the free ligand and its complexes was evaluated against the human carcinoma cell line (Caco‐2) by the MTT method and the IC50 values were calculated for all of them. Due to the presence of pyrazole rings in the structure of the ligand and its complexes, these materials have a substantial potential to inhibit cancer cell metastasis. The energetic stabilization due to donor‐acceptor interactions in terms of the natural bond orbital (NBO) analyses and nonlinear optical properties were also examined by using the DFT calculations. [ABSTRACT FROM AUTHOR]

Ras oncoproteins play a crucial role in the onset, maintenance, and progression of the most common and deadly human cancers. Despite extensive research efforts, only a few mutant-specific Ras inhibitors have been reported. We show that cmp4–previously identified as a water-soluble Ras inhibitor– targets multiple steps in the activation and downstream signaling of different Ras mutants and isoforms. Binding of this pan-Ras inhibitor to an extended Switch II pocket on HRas and KRas proteins induces a conformational change that down-regulates intrinsic and GEF-mediated nucleotide dissociation and exchange and effector binding. A mathematical model of the Ras activation cycle predicts that the inhibitor severely reduces the proliferation of different Ras-driven cancer cells, effectively cooperating with Cetuximab to reduce proliferation even of Cetuximab-resistant cancer cell lines. Experimental data confirm the model prediction, indicating that the pan-Ras inhibitor is an appropriate candidate for medicinal chemistry efforts tailored at improving its currently unsatisfactory affinity.