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Leishmaniasis and trypanosomiasis are parasitic diseases that are closely linked to poverty, pose significant local burdens, and are common in tropical and subtropical regions. Various synthetic tetralone derivatives were studied as potential scaffolds for antileishmanial and antitrypanosomal activities. The compounds were studied for their effectiveness against multiple kinetoplastid protozoan pathogens: Leishmania major, Leishmania mexicana, and bloodstream trypomastigotes of Trypanosoma brucei brucei. Two different strains of T. b. brucei were used. The first strain was the wild-type Trypanosoma brucei (s427-WT), and the second strain was the multidrug resistant (MDR) strain B48, which was produced by deleting the TbAT1 gene from s427WT and subsequent adaptation to high levels of resistance to diamidines and organo-arsenical drugs. Compounds 4c, 7c, 9b, and 11b showed activity against two strains of Trypanosoma and two different Leishmania species, establishing them as versatile leads with broad anti-kinetoplastid activity. Compound 4c, a tetralone derivative with a bromo-containing trimethoxybenzylidene moiety and methyl-substituted cyclohexanone ring, was identified as the most potent inhibitor for both T. b. brucei strains, with EC 50 values of 0.19 and 0.22 µM for WT and B48, respectively, showing the absence of cross-resistance with the diamidine and arsenical trypanocide classes. In addition, compound 4c exhibited more potency than both controls, eflornithine and pentamidine, against the MDR strain. We conclude that tetralone derivates could be a valuable starting point for the discovery of new antiparasitic drugs., (© 2025 Wiley Periodicals LLC.)

The current study aimed to generate a sulfhydryl-modified β-cyclodextrin-silymarin complex (sulfhydryl-modified β-CD-SMN complex) and to evaluate the enchantment in solubility, permeability, and bioavailability of a model BCS Class IV drug silymarin (SMN). For this purpose, sulfhydryl-modified β-CD was synthesized by replacing all primary and secondary -OH groups at the β-CD backbone with sulfhydryl groups via a novel microwave-assisted technique. Afterward, sulfhydryl-modified β-CD was complexed with silymarin and characterized by FTIR and 1 H NMR spectroscopy. Moreover, no. of sulfhydryl groups and their oxidative stability, solubility, safety, mucoadhesion, release, diffusion, and rheological studies were performed. Furthermore, in-vivo studies were conducted to confirm enhanced pharmacokinetic properties of silymarin. Sulfhydryl-modified β-CD showed 8291 ± 418 μmol/g sulfhydryl groups that were prone to oxidation at pH ≥ 5, however, most of the sulfhydryl groups were found stable at pH 4 having a pKa value of 8.3. Modified β-CD oligomer showed improved solubility of SMN, significantly enhanced drug transport across goat intestinal mucosa, 78-fold improved mucoadhesion, improved drug dissolution and 4.4-fold enhanced dynamic viscosity. No toxic effects were reported to Caco-2 cells at 0.5% (m/v) concentration of sulfhydryl-modified β-CD for 24 h. The apparent permeability coefficient (P app ) of SMN was 6.9-fold enhanced on goat intestinal mucosa. Moreover, in-vivo studies confirmed a significantly enhanced oral bioavailability of SMN due to combination with sulfhydryl-modified β-CD. Based on these findings, the sulfhydryl-modified β-CD-silymarin inclusion complex can be a promising technique to enhance the bioavailability of BCS Class IV drugs via enhanced solubility, mucoadhesion, and permeability triple action., 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.)

The present review is novel as it discusses the main findings of researchers on the topic and their implications, as well as highlights the emerging research in this particular area and its future prospective. The seeds of Flax (Linum usitatissimum) extrude mucilage (FSM) that has a diverse and wide range of applications, especially in the food industry and as a pharmaceutical ingredient. FSM has been blended with several food and dairy products to improve gelling ability, optical properties, taste, and user compliance. The FSM is recognized as a foaming, encapsulating, emulsifying, suspending, film-forming, and gelling agent for several pharmaceutical preparations and healthcare materials. Owing to stimuli (pH) -responsive swelling-deswelling characteristics, high swelling indices at different physiological pHs of the human body, and biocompatibility, FSM is considered a smart material for intelligent, targeted, and controlled drug delivery applications through conventional and advanced drug delivery systems. FSM has been modified through carboxymethylation, acetylation, copolymerization, and electrostatic complexation to get the desired properties for pharma, food, and healthcare products. The present review is therefore devoted to the isolation techniques, structural characterization, highly valuable properties for food and pharmaceutical industries, preclinical and clinical trials, pharmacological aspects, biomedical attributes, and patents of FSM., 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.)

The use of plant seed-based hydrogels to design drug delivery systems (DDSs) has increased due to their swellable, pH-responsive, biocompatible, biodegradable, and non-toxic nature. Herein, the chia seeds hydrogel (CSH) was extracted through an aqueous extraction method to explore its pH and salt-responsive swelling behavior and sustained release potential. The CSH was characterized using Fourier transform infrared (FT-IR) and solid-state cross-polarization magic angle spinning carbon-13 nuclear magnetic resonance (solid/state CP-MAS 13 C/NMR) spectra. Thermal analysis indicated that the CSH is a thermally stable material and decomposes in two steps. The scanning electron microscope (SEM) images of CSH witnessed the existence of microscopic channeling and a superporous nature with average pore sizes of 18 ± 11 μm (transverse cross-sections) and 23 ± 15 μm (longitudinal cross-sections). The CSH is a haemocompatible material. The CSH revealed pH and saline-responsive swelling in powder and compressed form (tablet) in the following order; distilled water (DW) > pH 7.4 > pH 6.8 > pH 1.2. Moreover, the swelling of CSH followed second-order kinetics. The swelling of CSH powder and tablets was decreased with increasing salt concentration. The pH, solvent, and saline responsive on/off switching (swelling/deswelling) results of the CSH and tablets disclosed its stimuli-responsive nature. The CSH prolonged the release of valsartan for 5 h at pH 7.4, whereas, negligible release (19.3%) was noted at pH 1.2. The valsartan release followed first-order kinetics and the non-Fickian diffusion. In conclusion, the CSH is a stimuli-responsive smart material with great potential to develop pH-sensitive and targeted DDSs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The prevention and treatment of microbial infections is an imminent global public health concern due to the poor antimicrobial performance of the existing antimicrobial regime and rapidly emerging antibiotic resistance in pathogenic microbes. In order to overcome these problems and effectively control bacterial infections, various new treatment modalities have been identified. To attempt this, various micro- and macro-molecular antimicrobial agents that function by microbial membrane disruption have been developed with improved antimicrobial activity and lesser resistance. Antimicrobial nanoparticle-hydrogels systems comprising antimicrobial agents (antibiotics, biological extracts, and antimicrobial peptides) loaded nanoparticles or antimicrobial nanoparticles (metal or metal oxide) constitute an important class of biomaterials for the prevention and treatment of infections. Hydrogels that incorporate nanoparticles can offer an effective strategy for delivering antimicrobial agents (or nanoparticles) in a controlled, sustained, and targeted manner. In this review, we have described an overview of recent advancements in nanoparticle-hydrogel hybrid systems for antimicrobial agent delivery. Firstly, we have provided an overview of the nanoparticle hydrogel system and discussed various advantages of these systems in biomedical and pharmaceutical applications. Thereafter, different hybrid hydrogel systems encapsulating antibacterial metal/metal oxide nanoparticles, polymeric nanoparticles, antibiotics, biological extracts, and antimicrobial peptides for controlling infections have been reviewed in detail. Finally, the challenges and future prospects of nanoparticle-hydrogel systems have been discussed., Competing Interests: “The authors declare no conflicts of interest.”, (This journal is © The Royal Society of Chemistry.)

Objectives: This study aimed to develop, optimize and evaluate glyceryl monooleate (GMO) based cubosomes as a drug delivery system containing cisplatin for treatment of human lung carcinoma., Significance: The significance of this research was to successfully incorporate slightly water soluble and potent anticancer drug (cisplatin) into cubosomes, which provide slow and sustained release of drug for longer period of time., Methods: The delivery system was developed through top-down approach by melting GMO and poloxamer 407 (P407) at 70 °C and then drop-wise addition of warm deionized water (70 °C) containing cisplatin. The formulation then exposed to probe sonicator for about 2 min. A randomized regular two level full factorial design with help of Design Expert was used for optimization of blank cubosomal formulations. Cisplatin loaded cubosomes were then subjected to physico-chemical characterization., Results: The characterization of the formulation revealed that it had a sufficient surface charge of -9.56 ± 1.33 mV, 168.25 ± 5.73 nm particle size, and 60.64 ± 0.11% encapsulation efficiency. The in vitro release of cisplatin from the cubosomes at pH 7.4 was observed to be sustained, with 94.5% of the drug being released in 30 h. In contrast, 99% of cisplatin was released from the drug solution in just 1.5 h. In vitro cytotoxicity assay was conducted on the human lung carcinoma NCI-H226 cell line, the cytotoxicity of cisplatin-loaded cubosomes was relative to that of pure cisplatin solution, while blank (without cisplatin) cubosomes were nontoxic., Conclusions: The obtained results demonstrated the successful development of cubosomes for sustained delivery of cisplatin.

The current research was planned to enhance the bioavailability of hydrophobic drug after oral administration through the development of a nanoparticle drug delivery system (DDS). Therefore, febuxostat-loaded chitosan nanoparticles (FLC NPs) were prepared using a modified ionic gelation method and optimized the reaction conditions through the design of experiments. Design expert software was used to check the desirability of the central composite design and the interactive effects of the independent variables (chitosan concentration, ratio of chitosan to linker, and pH of the medium) on the response variables (size distribution, zeta potential, polydispersity index (PDI), and entrapment efficiency (EE)) of FLC NPs. All ingredients of the optimized formulation (formulation Q) were compatible with each other as evident from FTIR, PXRD, and TGA studies, and displayed 234.7 nm particle size, 0.158 PDI, 25.8 mV zeta potential, and 76.9 % EE. TEM, SEM, and AFM exhibited a smooth, dense, and uniform structure without any visible pores in the structure of FLC NPs. The in vitro and in vivo drug release studies described a sustained release pattern of febuxostat and increased relative bioavailability by 286.63 %. Considering these findings, this chitosan nanoparticle DDS can further be used for improving the EE and bioavailability of hydrophobic drugs., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Lung cancer is the one of the most prevalent cancer in the world. It kills more people from cancer than any other cause and is especially common in underdeveloped nations. With 1.2 million instances, it is also the most prevalent cancer in men worldwide, making about 16.7% of the total cancer burden. Surgery is the main form of curative treatment for early-stage lung cancer. However, the majority of patients had incurable advanced non-small cell lung cancer (NSCLC) recurrence after curative purpose surgery, which is indicative of the aggressiveness of the illness and the dismal outlook. The gold standard of treatment for NSCLC patients includes drug targeting of specific mutated genes drive in development of lung cancer. Furthermore, patients with advanced NSCLC and those with early-stage illness needing adjuvant therapy should use cisplatin as it is the more active platinum drug. So, this review encompasses the non-small cell lung cancer microenvironment, treatment approaches, and use of cisplatin as a first-line regimen for NSCLC, its mechanism of action, cisplatin resistance in NSCLC and also the prevention strategies to revert the drug resistance., 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 article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A new series of 2-aminobenzothiazole hybrids linked to thiazolidine-2,4-dione 4a-e , 1,3,4-thiadiazole aryl urea 6a-d, and cyanothiouracil moieties 8a-d was synthesised. The in vitro antitumor effect of the new hybrids was assessed against three cancer cell lines, namely, HCT-116, HEPG-2, and MCF-7 using Sorafenib (SOR) as a standard drug. Among the tested compounds, 4a was the most potent showing IC50 of 5.61, 7.92, and 3.84 µM, respectively. Furthermore, compounds 4e and 8a proved to have strong impact on breast cancer cell line with IC50 of 6.11 and 10.86 µM, respectively. The three compounds showed a good safety profile towards normal WI-38 cells. Flow cytometric analysis of the three compounds in MCF-7 cells revealed that compounds 4a and 4c inhibited cell population in the S phase, whereas 8a inhibited the population in the G1/S phase. The most promising compounds were subjected to a VEGFR-2 inhibitory assay where 4a emerged as the best active inhibitor of VEGFR-2 with IC50 91 nM, compared to 53 nM for SOR. In silico analysis showed that the three new hybrids succeeded to link to the active site like the co-crystallized inhibitor SOR.

Applying a multistep approach, novel indolin-2-ones (IND) that possess an arylidene motif have been synthesized. Eight compounds were chosen for different biological tests (antimicrobial and cytotoxicity). IND containing 2-thienyl (4h) fragment have been found to exhibit good antimicrobial activity against B. cereus . Molecules that have 3-aminophenyl (4d) or 2-pyridyl (4g) groups have shown the best antifungal activities against all tested fungi. These compounds have also been noticed as promising pharmaceuticals against MCF-7 cancer cell lines. Experimental outcomes from the investigation of the interaction of 4d with DNA implied its moderate binding to DNA ( K SV = 1.35 × 10 4 and 3.05 × 10 4 M -1 for EB and Hoechst binder, respectively). However, considerably stronger binding of 4d to BSA has been evidenced ( K a = 6.1 × 10 6 M -1 ). In summary, IND that contains m -aminobenzylidene fragment (4d) exhibits a good dual biological activity making it a promising candidate for further investigation in the drug discovery sector., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The current research work focuses on the extraction and optimization of the hydrogel (AVM) from the seeds of Artemisia vulgaris using Box-Behnken design-response surface methodology (BBD-RSM). The AVM was obtained through a hot water extraction process. The influence of different factors, including pH (U = 4 to 10), temperature (V = 25 to 110 °C), seed/water ratio, i.e., S/W ratio (W = 1/10 to 1/70 w / v ), and seed/water contact time, i.e., S/W time (X = 1 to 12 h) on the yield of AVM was evaluated. The p -value for the analysis of variance (ANOVA) was found to be <0.001, indicating that the yield of AVM mainly depended on the abovementioned factors. The highest yield of AVM, i.e., 15.86%, was found at a pH of 7.12, temperature of 80.04 °C, S/W ratio of 1/33.24 w / v , and S/W time of 8.73 h according to Design-Expert Software. The study of the pH-responsive behavior of AVM in tablet form (formulation AVT3) revealed that AVM is a pH-responsive material with significantly high swelling at pH 7.4. However, less swelling was witnessed at pH 1.2. Moreover, AVM was found to be a sustained release material for esomeprazole at pH 7.4 for 12 h. The drug release from AVT3 was according to the super case-II transport mechanism and zero-order kinetics.

New phthalazone tethered 1,2,3-triazole derivatives 12-21 were synthesized utilizing the Cu(I)-catalyzed click reactions of alkyne-functionalized phthalazone 1 with functionalized azides 2-11. The new phthalazone-1,2,3-triazoles structures 12-21 were confirmed by different spectroscopic tools, like IR; 1 H, 13 C, 2D HMBC and 2D ROESY NMR; EI MS, and elemental analysis. The antiproliferative efficacy of the molecular hybrids 12-21 against four cancer cell lines was evaluated, including colorectal cancer, hepatoblastoma, prostate cancer, breast adenocarcinoma, and the normal cell line WI38. The antiproliferative assessment of derivatives 12-21 showed potent activity of compounds 16, 18, and 21 compared to the anticancer drug doxorubicin. Compound 16 showed selectivity (SI) towardthe tested cell lines ranging from 3.35 to 8.84 when compared to Dox., that showed SI ranged from 0.75 to 1.61. Derivatives 16, 18 and 21 were assessed towards VEGFR-2 inhibitory activity and result in that derivative 16 showed the potent activity (IC 50  = 0.123 µM) in comparison with sorafenib (IC 50  = 0.116 µM). Compound 16 caused an interference with the cell cycle distribution of MCF7 and increased the percentage of cells in S phase by 1.37-fold. In silico molecular docking of the effective derivatives 16, 18, and 21 against vascular endothelial growth factor receptor-2 (VEGFR-2) confirmed the formation of stable protein-ligand interactions within the pocket., 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 © 2023 Elsevier Inc. All rights reserved.)

In the presented study, eight novel Meldrum's acid derivatives containing various vanillic groups were synthesized. Vanillidene Meldrum's acid compounds were tested against different cancer cell lines and microbes. Out of nine, three showed very good biological activity against E. coli , and HeLa and A549 cell lines. It is shown that the O -alkyl substituted derivatives possessed better antimicrobial and anticancer activities in comparison with the O -acyl ones. The decyl substituted molecule ( 3i ) has the highest activity against E. coli (MIC = 12.4 μM) and cancer cell lines (HeLa, A549, and LS174 = 15.7, 21.8, and 30.5 μM, respectively). The selectivity index of 3i is 4.8 (HeLa). The molecular docking study indicates that compound 3i showed good binding affinity to DNA, E. coli Gyrase B, and topoisomerase II beta. The covalent docking showed that 3i was a Michael acceptor for the nucleophiles Lys and Ser. The best E b was noted for the topoisomerase II beta-LYS482- 3i cluster.

Background: Extensively drug-resistant (XDR) Salmonella enterica serovar Typhi (S. Typhi) poses a grave threat to public health due to increased mortality and morbidity caused by typhoid fever. Honey is a promising antibacterial agent, and we aimed to determine the antibacterial activity of honey against XDR S. Typhi., Methods: We isolated 20 clinical isolates of XDR S. Typhi from pediatric septicemic patients and determined the minimum inhibitory concentrations (MICs) of different antibiotics against the pathogens using the VITEK 2 Compact system. Antimicrobial-resistant genes carried by the isolates were identified using PCR. The antibacterial efficacy of five Pakistani honeys was examined using agar well diffusion assay, and their MICs and minimum bactericidal concentrations (MBCs) were determined with the broth microdilution method., Results: All 20 isolates were confirmed as S. Typhi. The antibiogram phenotype was confirmed as XDR S. Typhi with resistance to ampicillin (≥ 32 µg/mL), ciprofloxacin (≥ 4 µg/mL), and ceftriaxone (≥ 4 µg/mL) and sensitivity to azithromycin (≤ 16 µg/mL) and carbapenems (≤ 1 µg/mL). Molecular conformation revealed the presence of bla TM-1 , Sul1, qnrS, gyrA, gyrB, and bla CTX-M-15 genes in all isolates. Among the five honeys, beri honey had the highest zone of inhibition of 7-15 mm and neem honey had a zone of inhibition of 7-12 mm. The MIC and MBC of beri honey against 3/20 (15%) XDR S. Typhi isolates were 3.125 and 6.25%, respectively, while the MIC and MBC of neem were 3.125 and 6.25%, respectively, against 3/20 (15%) isolates and 6.25 and 12.5%, respectively, against 7/20 (35%) isolates., Conclusion: Indigenous honeys have an effective role in combating XDR S. Typhi. They are potential candidates for clinical trials as alternative therapeutic options against XDR S. Typhi isolates., (© 2023. The Author(s).)

Covalent organic frameworks (COFs), synthesized from organic monomers, are porous crystalline polymers. Monomers get attached through strong covalent bonds to form 2D and 3D structures. The adjustable pore size, high stability (chemical and thermal), and metal-free nature of COFs make their applications wider. This review article briefly elaborates the synthesis, types, and applications (catalysis, environmental Remediation, sensors) of COFs. Furthermore, the applications of COFs as biomaterials are comprehensively discussed. There are several reported COFs having good results in anti-cancer and anti-bacterial treatments. At the end, some newly reported COFs having anti-viral and wound healing properties are also discussed., Competing Interests: The authors declare no conflict of interest.

Background: The use of synthetic and semi-synthetic materials in drug delivery systems has associated drawbacks like costly synthesis, toxicity, and biocompatibility issues. Therefore, there is a need to introduce novel materials to overcome such issues. Naturally occurring and water-swellable polysaccharides are advantageous in overcoming the above-mentioned issues. Therefore, we are reporting a novel hydrogel (SSH) isolated from the seeds of Salvia spinosa as a sustained release material., Methods: SSH was explored for its pH-dependent and salt-responsive swelling before and after compression in a tablet form. Stimuli-responsive swelling and deswelling were also monitored at pH 7.4 and pH 1.2 in deionized water (DW) and normal saline and DW and ethanol. The sustained-release potential of SSH-based tablets was monitored at gastrointestinal tract (GIT) pH. The transit of SSH tablets was ascertained through an X-ray study., Results: The swelling of SSH in powder and tablet form was found in the order of DW > pH 7.4 > pH 6.8 > pH 1.2. An inverse relation was found between the swelling of SSH and the concentration of the salt solution. The SSH showed stimuli-responsive swelling and de-swelling before and after compression, indicating the unaltered nature of SSH even in a closely packed form, i.e., tablets. Sustained release of theophylline (< 80%) was witnessed at pH 6.8 and 7.4 during the 12 h study following zeroorder kinetics, and radiographic images also showed 9 h retention in GIT., Conclusion: These investigations showed the potential of SSH as a pH-sensitive material for sustained and targeted drug delivery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Benzocycloheptanone is the main structural feature of numerous famous natural pharmacophores such as Colchicine and Theaflavins. It has gained popularity in the field of medicinal chemistry, attributing to its broad-spectrum effect., Objective: Numerous research publications addressing the derivatization of the benzosuberone molecule have been published, and their biological and pharmacological features have been extensively addressed. Numerous derivatives have been discovered as lead compounds for the development of novel medications. Thus, the goal of this article is to summarize and analyze all published findings on the synthesis and biological assessment of the benzosuberone skeleton., Methods: All main databases including SciFinder, PubMed and google scholar were used with appropriate keywords to select related reported literature, and further bibliography in related literature was also used to find linked reports., Results: Synthetic routes to benzosuberone-based ring systems were identified from the literature and explained stepwise and after this, pharmacological activities of all benzosuberone derivatives are listed target-wise and a detailed structure-activity relationship is developed., Conclusion: The current review discusses numerous synthetic approaches for the synthesis of benzosuberone skeleton and its applications in many domains of medical chemistry. Compounds possessing the benzosuberone skeleton play an important role in the drug development process due to their wide range of biological actions such as anti-cancer, antibacterial, antifungal, antiinflammatory, and so on. The results of antibacterial screening and Structure-Activity Relationship (SAR) revealed that the compounds containing this skeleton with the piperazine and morpholine rings have antimicrobial potential when compared to the commercial antibiotic Norfloxacin. Despite extensive study to date, there is still room for the development of novel and efficient pharmacophores using the structure-based drug design technique., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Chalcones are precursors of flavonoids and exhibit a broad spectrum of pharmacological activity., Objective: As anti-inflammatory agents, two series of chalcone derivatives and chalcone-based oximes were synthesized and characterized. To integrate the tetramethylpyrazine moiety into these novel molecules, the multifunctional natural chemical ligustrazine was employed., Methods: A variety of newly synthesized ligustrazine-based chalcones were utilized as precursors for the synthesis of new oximes and their inhibitory activity against COX-1, COX-2, and LOX-5 enzymes were compared., Results: The conversion of ketones to their oxime derivatives increased the effectiveness of COX-1 and COX-2 inhibition. Due to the substituted ether groups, oxime derivative 5d had the lowest IC 50 values of 0.027 ± 0.004 μM and 0.150 ± 0.027 μM for COX-1 and COX-2 isoenzymes, respectively. Notably, the oxime derivative's highest effectiveness is conferred by the presence of methoxymethoxy or hydroxy groups at the C-3 and C-4 positions on the phenyl ring. The 6b derivative with a long alkyl chain ether group was shown to be the most powerful 5-LOX inhibitor. All compounds were also assessed for their ability to inhibit nitric oxide generation and LPS-induced IL-6, IL-1β, and TNF-α production in RAW 264.7 macrophages. Finally, in order to determine the structural effects responsible for the binding mechanism of compounds, they were docked into the binding sites of COX-1, COX-2, and 5-LOX, which revealed an inhibitory mechanism of action and demonstrated the relevance of various types of interactions., Conclusion: The findings showed that these novel compounds had a significant impact on antiinflammatory actions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Rubella virus (RuV) generally causes a mild infection, but it can sometimes lead to systemic abnormalities. This study aimed to conduct a bibliometric analysis of over two decades of RuV research. Medical studies published from 2000 to 2021 were analyzed to gain insights into and identify research trends and outputs in RuV. R and VOSviewer were used to conduct a bibliometric investigation to determine the globally indexed RuV research output. The Dimensions database was searched with RuV selected as the subject, and 2500 published documents from the preceding two decades were reviewed. The number of publications on RuV has increased since 2003, reaching its peak in 2020. There were 12,072 authors and 16,769 author appearances; 88 publications were single-authored and 11,984 were multi-authored. The United States was the most influential contributor to RuV research, in terms of publications and author numbers. The number of RuV-related articles has continued to increase over the past few years due to the significant rubella burden in low-income nations. This study will aid in formulating plans and policies to control and prevent RuV infections.

The dose frequency of drugs belonging to class II is usually high and associated with harmful effects on the body. The study aimed to enhance the solubility of the poorly water-soluble drug amoxicillin (AM) by the solid dispersion (SD) technique. Six different SDs of AM, F1-F6, were prepared by the spray drying technique using two other carriers, HP-β-CD (F1-F3) and HPMC (F4-F6), in 1:1, 1:2, and 1:3 drug-to-polymer ratios. These SDs were analyzed to determine their practical yield, drug content, and aqueous solubility using analytical techniques such as Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, and powder X-ray diffraction. The effect of polymer concentration on SDs was determined using aqueous solubility, in vitro dissolution, and in vivo studies. The results showed no drug-polymer interactions in SDs. Solubility studies showed that SDs based on the drug-to-polymer ratio of 1:2 (F2 and F5) were highly soluble in water compared to those with ratios of 1:1 and 1:3. In vitro dissolution studies also showed that SDs with a ratio of 1:2 released the highest drug concentration from both polymeric systems. The SDs based on HPMC confirmed the more sustained release of the drug as compared to that of HP-β-CD. All the SDs were observed as stable and amorphous, with a smooth spherical surface. In vivo studies reveal the enhancement of pharmacokinetics parameters as compared to standard AM. Hence, it is confirmed that spray drying is an excellent technique to enhance the solubility of AM in an aqueous medium. This may contribute to the enhancement of the pharmacokinetic behaviors of SDs., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

A new series of indoline-2-one derivatives was designed and synthesized based on the essential pharmacophoric features of VEGFR-2 inhibitors. Anti-proliferative activities were assessed for all derivatives against breast (MCF-7) and liver (HepG2) cancer cell lines, using sunitinib as a reference agent. The most potent anti-proliferative derivatives were evaluated for their VEGFR-2 inhibition activity. The effects of the most potent inhibitor, 17a , on cell cycle, apoptosis, and expression of apoptotic markers (caspase-3&-9, BAX, and Bcl-2) were studied. Molecular modeling studies, such as docking simulations, physicochemical properties prediction, and pharmacokinetic profiling were performed. The results revealed that derivatives 5b , 10e , 10g , 15a , and 17a exhibited potent anticancer activities with IC 50 values from 0.74-4.62 µM against MCF-7 cell line (sunitinib IC 50 = 4.77 µM) and from 1.13-8.81 µM against HepG2 cell line (sunitinib IC 50 = 2.23 µM). Furthermore, these compounds displayed potent VEGFR-2 inhibitory activities with IC 50 values of 0.160, 0.358, 0.087, 0.180, and 0.078 µM, respectively (sunitinib IC 50 = 0.139 µM). Cell cycle analysis demonstrated the ability of 17a to induce a cell cycle arrest of the HepG2 cells at the S phase and increase the total apoptosis by 3.5-fold. Moreover, 17a upregulated the expression levels of apoptotic markers caspase-3 and -9 by 6.9-fold and 3.7-fold, respectively. In addition, 17a increased the expression level of BAX by 2.7-fold while decreasing the expression level of Bcl-2 by 1.9-fold. The molecular docking simulations displayed enhanced binding interactions and similar placement as sunitinib inside the active pocket of VEGFR-2. The molecular modeling calculations showed that all the test compounds were in accordance with Lipinski and Veber rules for oral bioavailability and had promising drug-likeness behavior.

The monkeypox virus (MPXV) is the cause of a zoonotic infection similar to smallpox. Although it is endemic to Africa, it has recently begun to circulate in other parts of the world. In July 2022, the World Health Organization declared monkeypox an international public health emergency. This review aims to provide an overview of this neglected zoonotic pathogen. MPXV circulates as two distinct clades, the Central African and West African, with case fatality rates of 10.6% and 3.6%, respectively. The risk of infection is greater for those who work with animals or infected individuals. The virus' entry into the human body provokes both natural and acquired immunity. Although natural killer cells, CD4 + T cells, and CD8 + T cells play an essential role in eradicating MPXV, there is still a gap in the understanding of the host immune response to the virus. Currently, there are no specific therapeutic guidelines for treating monkeypox; however, some antiviral drugs such as tecovirimat and cidofovir may help to abate the severity of the disease. The use of nonpharmaceutical interventions and immunization can reduce the risk of infection. Increased surveillance and identification of monkeypox cases are crucial to understand the constantly shifting epidemiology of this resurging and intimidating disease. The present review provides a detailed perspective on the emergence and circulation of MPXV in human populations, infection risks, human immune response, disease diagnosis and prevention strategies, and future implications, and highlights the importance of the research community engaging more with this disease for an effective global response., (Copyright © 2022. Published by Elsevier Ltd.)

Human respiratory infections caused by coronaviruses can range from mild to deadly. Although there are numerous studies on coronavirus disease 2019 (COVID-19), few have been published on its Omicron variant. In order to remedy this deficiency, this study undertook a bibliometric analysis of the publishing patterns of studies on the Omicron variant and identified hotspots. Automated transportation, environmental protection, improved healthcare, innovation in banking, and smart homes are just a few areas where machine learning has found use in tackling complicated problems. The sophisticated Scopus database was queried for papers with the term "Omicron" in the title published between January 2020 and June 2022. Microsoft Excel 365, VOSviewer, Bibliometrix, and Biblioshiny from R were used for a statistical analysis of the publications. Over the study period, 1917 relevant publications were found in the Scopus database. Viruses was the most popular in publications for Omicron variant research, with 150 papers published, while Cell was the most cited source. The bibliometric analysis determined the most productive nations, with USA leading the list with the highest number of publications (344) and the highest level of international collaboration on the Omicron variant. This study highlights scientific advances and scholarly collaboration trends and serves as a model for demonstrating global trends in Omicron variant research. It can aid policymakers and medical researchers to fully grasp the current status of research on the Omicron variant. It also provides normative data on the Omicron variant for visualization, study, and application.

In this study new sulphamethoxazole derivatives ( S1 - S4 , S6 - S12 , and S14 - S22 ) were designed and synthesized and their structures were fully characterized and validated using NMR, mass, and IR spectroscopy, as well as elemental analyses. All new derivatives ( S1 - S22 ) were assayed against human carbonic anhydrase (hCAs IX and XII) for their inhibitory activities. hCAs IX and XII were chosen due to the fact that CAIX expression is recognized as a hypoxia marker with a poor prognosis in breast cancer. When compared to Dorzolamide HCl as a standard reference, derivatives S2 , S3 , S8 , S9 , and S15 had the most effective inhibition with low IC 50 values. The active compounds were further evaluated against hCAs I and II inhibitory activity and compounds S8 , S9 and S15 showed the least inhibitory effect compared to the reference standard, acetazolamide, indicating that their effect in normal cells is the lowest. Cell viability tests for the selected compounds were carried out on MCF7 (normoxia and hypoxia) and on the normal breast cell line (MCF10a) with Staurosporine as a standard. The results showed that compound S15 had a highly potent cytotoxic effect. Furthermore, cell cycle analysis results showed that compound S15 triggered cell cycle arrest and apoptosis in G1/S of MCF7 cancer cells. Finally, molecular docking was performed to point out the possible explanation for the vital structural features and key-interactions exerted by our ligands with h CAs IX and XII that might share additional designs and highlight possible leads for a hopeful anticancer agent. Consequently, sulphamethoxazole Derivative S15 could be the potential lead for emerging selective cytotoxic compounds directing h CAs IX and XII.

Foodborne pathogens have acquired the ability to produce biofilms to survive in hostile environments. This study evaluated biofilm formation, antimicrobial resistance (AMR), and heavy metal tolerance of bacteria isolated from dairy and non-dairy food products. We aseptically collected and processed 200 dairy and non-dairy food specimens in peptone broth, incubated them overnight at 37 °C, and sub-cultured them on various culture media. Bacterial growth was identified with biochemical tests and API 20E and 20NE strips. The AMR of the isolates was observed against different antibacterial drug classes. Biofilm formation was detected with the crystal violet tube method. Heavy metal salts were used at concentrations of 250−1500 µg/100 mL to observe heavy metal tolerance. We isolated 180 (50.4%) bacteria from dairy and 177 (49.6%) from non-dairy food samples. The average colony-forming unit (CFU) count for dairy and non-dairy samples was 2.9 ± 0.9 log CFU/mL and 5.1 ± 0.3 log CFU/mL, respectively. Corynebacterium kutscheri (n = 74), lactobacilli (n = 73), and Staphylococcus aureus (n = 56) were the predominant Gram-positive and Shigella (n = 10) the predominant Gram-negative bacteria isolated. The correlation between biofilm formation and AMR was significant (p < 0.05) for most cephalosporins, aminoglycosides, and fluoroquinolones. Heavy metal tolerance tended to be higher in biofilm producers at different metal concentrations. The pathogens isolated from dairy and non-dairy food showed a high burden of AMR, high propensity for biofilm formation, and heavy metal tolerance, and pose an imminent threat to public health.

Objective: Mentha (M.) longifolia (L.) is traditionally used for various ailments. The current study was intended to explore the underlying vasorelaxation mechanisms of M. longifolia., Material and Methods: Aqueous-methanol extract from the aerial parts of M. longifolia was prepared and subjected to activity-guided fractionation. The vasorelaxant activity was performed using porcine coronary arteries with intact and denuded endothelium. In-vitro PDE inhibitory activity of the active fraction was carried out using the radio-enzymatic assay. The active fraction was also subjected to GCMS. Docking and molecular dynamic simulation studies were also performed RESULT: We had observed that aqueous-methanolic extract induced relaxation in the coronary artery in a dose-dependent manner when the endothelium was intact and denuded. n-butanol fraction (MLB) has produced a maximum effect, and it was selected for mechanistic studies. MLB has significantly enhanced the relaxation produced by cAMP and cGMP, elevating atrial natriuretic peptide, sodium nitroprusside, isoproterenol, and forskolin. The pre-treatment with MLB inhibited the contractile response produced by KCl, U46619, and CaCl 2 in without endothelium rings. MLB has non-selectively inhibited the PDE isoforms. GCMS analysis of MLB has revealed the presence of menthol, thymol, and carvacrol in the active fraction. Docking and molecular dynamic simulation studies have indicated that thymol can be a competitive inhibitor for PDE1., Conclusion: It is postulated that an n-butanol fraction of Mentha longifolia produced endothelium-independent relaxation due to increased levels of cAMP and cGMP caused by the inhibition of various PDEs., Competing Interests: Conflict of interest statement We confirm that there are no known conflicts of interest associated with this publication, (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The emergence of carbapenem-resistant Acinetobacter calcoaceticus - baumannii complex (CRACB) in clinical environments is a significant global concern. These critical pathogens have shown resistance to a broad spectrum of antibacterial drugs, including carbapenems, mostly due to the acquisition of various β-lactamase genes. Clinical samples (n = 1985) were collected aseptically from multiple sources and grown on blood and MacConkey agar. Isolates and antimicrobial susceptibility were confirmed with the VITEK-2 system. The modified Hodge test confirmed the CRACB phenotype, and specific PCR primers were used for the molecular identification of bla OXA and bla NDM genes. Of the 1985 samples, 1250 (62.9%) were culture-positive and 200 (43.9%) were CRACB isolates. Of these isolates, 35.4% were recovered from pus samples and 23.5% from tracheal secretions obtained from patients in intensive care units (49.3%) and medical wards (20.2%). An antibiogram indicated that 100% of the CRACB isolates were resistant to β-lactam antibiotics and β-lactam inhibitors, 86.5% to ciprofloxacin, and 83.5% to amikacin, while the most effective antibiotics were tigecycline and colistin. The CRACB isolates displayed resistance to eight different AWaRe classes of antibiotics. All isolates exhibited the bla OXA-51 gene, while bla OXA-23 was present in 94.5%, bla VIM in 37%, and bla NDM in 14% of the isolates. The bla OXA-51 , bla OXA-23 , and bla OXA-24 genes co-existed in 13 (6.5%) isolates. CRACB isolates with co-existing bla OXA-23 , bla OXA-24 , bla NDM , bla OXA-51 and bla VIM genes were highly prevalent in clinical samples from Pakistan. CRACB strains were highly critical pathogens and presented resistance to virtually all antibacterial drugs, except tigecycline and colistin.

Alzheimer's disease (AD) is a severe neurodegenerative disorder of the brain that manifests as dementia, disorientation, difficulty in speech, and progressive cognitive and behavioral impairment. The emerging therapeutic approach to AD management is the inhibition of β-site APP cleaving enzyme-1 (BACE1), known to be one of the two aspartyl proteases that cleave β-amyloid precursor protein (APP). Studies confirmed the association of high BACE1 activity with the proficiency in the formation of β-amyloid-containing neurotic plaques, the characteristics of AD. Only a few FDA-approved BACE1 inhibitors are available in the market, but their adverse off-target effects limit their usage. In this paper, we have used both ligand-based and target-based approaches for drug design. The QSAR study entails creating a multivariate GA-MLR (Genetic Algorithm-Multilinear Regression) model using 552 molecules with acceptable statistical performance ( R 2 = 0.82, Q 2 loo = 0.81). According to the QSAR study, the activity has a strong link with various atoms such as aromatic carbons and ring Sulfur, acceptor atoms, sp2-hybridized oxygen, etc. Following that, a database of 26,467 food compounds was primarily used for QSAR-based virtual screening accompanied by the application of the Lipinski rule of five; the elimination of duplicates, salts, and metal derivatives resulted in a truncated dataset of 8,453 molecules. The molecular descriptor was calculated and a well-validated 6-parametric version of the QSAR model was used to predict the bioactivity of the 8,453 food compounds. Following this, the food compounds whose predicted activity (pKi) was observed above 7.0 M were further docked into the BACE1 receptor which gave rise to the Identification of 4-(3,4-Dihydroxyphenyl)-2-hydroxy-1H-phenalen-1-one (PubChem I.D: 4468; Food I.D: FDB017657) as a hit molecule (Binding Affinity = -8.9 kcal/mol, pKi = 7.97 nM, Ki = 10.715 M). Furthermore, molecular dynamics simulation for 150 ns and molecular mechanics generalized born and surface area (MMGBSA) study aided in identifying structural motifs involved in interactions with the BACE1 enzyme. Molecular docking and QSAR yielded complementary and congruent results. The validated analyses can be used to improve a drug/lead candidate's inhibitory efficacy against the BACE1. Thus, our approach is expected to widen the field of study of repurposing nutraceuticals into neuroprotective as well as anti-cancer and anti-viral therapeutic interventions., Competing Interests: AA is honorary associated with the scientific board of the company AFNP Med in Austria. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mukerjee, Das, Jawarkar, Maitra, Das, Castrosanto, Paul, Samad, Zaki, Al-Hussain, Masand, Hasan, Bukhari, Perveen, Alghamdi, Alexiou, Kamal, Dey, Malik, Bakal, Abuzenadah, Ghosh and Md Ashraf.)

A novel multifunctional series of 3-aminobenzofuran derivatives 5a-p were designed and synthesized as potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The target compounds 5a-p were prepared via a three-step reaction, starting from 2-hydroxy benzonitrile. In vitro anti-cholinesterase activity exhibited that most of the compounds had potent acetyl- and butyrylcholinesterase inhibitory activity. In particular, compound 5f containing 2-fluorobenzyl moiety showed the best inhibitory activity. Furthermore, this compound showed activity on self- and AChE-induced Aβ-aggregation and MTT assay against PC12 cells. The kinetic study revealed that compound 5f showed mixed-type inhibition on AChE. Based on these results, compound 5f can be considered as a novel multifunctional structural unit against Alzheimer's disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hasanvand, Motahari, Nadri, Moghimi, Foroumadi, Ayati, Akbarzadeh, Bukhari and Foroumadi.)

The 5-hydroxytryptamine receptor 6 (5-HT6) has gained attention as a target for developing therapeutics for Alzheimer's disease, schizophrenia, cognitive dysfunctions, anxiety, and depression, to list a few. In the present analysis, a larger and diverse dataset of 1278 molecules covering a broad chemical and activity space was used to identify visual and concealed structural features associated with binding affinity for 5-HT6. For this, quantitative structure-activity relationships (QSAR) and molecular docking analyses were executed. This led to the development of a statistically robust QSAR model with a balance of excellent predictivity (R 2 tr = 0.78, R 2 ex = 0.77), the identification of unreported aspects of known features, and also novel mechanistic interpretations. Molecular docking and QSAR provided similar as well as complementary results. The present analysis indicates that the partial charges on ring carbons present within four bonds from a sulfur atom, the occurrence of sp3-hybridized carbon atoms bonded with donor atoms, and a conditional occurrence of lipophilic atoms/groups from nitrogen atoms, which are prominent but unreported pharmacophores that should be considered while optimizing a molecule for 5-HT6. Thus, the present analysis led to identification of some novel unreported structural features that govern the binding affinity of a molecule. The results could be beneficial in optimizing the molecules for 5-HT6.

The current study depicts the comparative effects of nanogel using Withania coagulans extract, pregabalin alone, and a co-combination gel. The gels prepared were then analyzed for conductivity, viscosity, spread ability, globule size, zeta potential, polydispersity index, and TEM. The globule size of the co-combination gel, determined by zeta sizer, was found to be (329 ± 0.573 nm). FTIR analysis confirms the successful development of gel, without any interaction. Drug distribution at the molecular level was confirmed by XRD. DSC revealed no bigger thermal changes. TEM images revealed spherical molecules with sizes of 200 nm for the co-combination gel. In vivo studies were carried out by infliction of third degree burn wounds on rat skin, and they confirmed that pregabalin and Withania coagulans heals the wound more effectively, with a wound contraction rate of 89.95%, compared to remaining groups. Anti-inflammatory activity (IL-6 and TNF-α), determined by the ELISA technique, shows that the co-combination gel group reduces the maximum inflammation with TNF-α value (132.2 pg/mL), compared to the control (140.22 pg/mL). Similarly, the IL-6 value was found to be (78 pg/mL) for the co-combination gel and (81 pg/mL) in the case of the control. Histopathologically, the co-combination gel heals wounds more quickly, compared to individual gel. These outcomes depict that a co-combination gel using plant extracts and drugs can be successfully used to treat burn injury.

A novel series of amides based TMP moiety was designed, synthesized and evaluated for their antiproliferative as well as enzyme inhibition activity. Compounds 6a and 6b showed remarkable cytotoxic activity against HepG2 cells with IC 50 values 0.65 and 0.92 μM, respectively compared with SAHA and CA-4 as reference compounds. In addition, compound 6a demonstrated good HDAC-tubulin dual inhibition activity as it showed better HDAC activity as well as anti-tubulin activity. Moreover, compound 6a exhibited G2/M phase arrest and pre-G1 apoptosis as demonstrated by cell cycle analysis and Annexin V assays. Further apoptosis studies demonstrated that compound 6a boosted the level of c aspase 3/7. C aspase 3/7 activation and apoptosis induction were evidenced by decrease in mitochondrial permeability suggesting that activation of c aspase 3/7 may occur via mitochondrial apoptotic pathway.

A series of novel Schiff bases-based TMP moieties have been designed and synthesized as potential anticancer agents. The target Schiff bases were screened for their cytotoxic activity against the MDA-MB-231 breast cancer cell line. Most of the tested molecules revealed good cytotoxic activity, especially compounds 4h, 4j and 5d. Being the most potent, compound 4h showed good tubulin polymerization inhibition activity as revealed by immunofluorescence analysis and ELISA assay. Additionally, compound 4h was screened for cell cycle disturbance and apoptosis induction. Pre-G1 apoptosis and cell growth halt at the G2/M phase were discovered to be caused by it. Moreover, compound 4h induced apoptosis via p53 and Bax activation, as well as reduced the level of Bcl-2. Additionally, the most potent compound 4h was lodged on nanostructured lipid carriers (NLCs). 23 full factorial design was involved to govern the influence of the fabrication variables on the in vitro characters of the casted NLCs. F3 was picked as the optimum formula exhibiting dominant desirability value 0.805, EE% 95.6 ± 2.4, PS 222.4 ±18.7, PDI 0.23 ± 0.05 and ZP −39.2 ± 3.9 Mv. Furthermore, F3 affirmed improved solubility and release over the drug suspension. In the comparative cytotoxic activity, F3 was capable of diminishing the IC50 by around 2.15 times for pure 4h, while nearly close to the IC50 of the reference drug. Thus, NLCs could be a potential platform for boosted antitumor activity.

The present study was conducted with an intent to evaluate the protective effect of butanolic fraction of Delphinium brunonianum on fructose mediated metabolic abnormalities in rats. Rats in all groups except control group were fed on 10% fructose for 6 weeks; however, rats in the treated group also received butanolic fraction for the last 3 weeks, along with the fructose. Moreover, phytoconstituents present in butanolic fraction were analyzed using LC-MS. All doses of butanolic fraction profoundly reduce the fructose-induced blood pressure, sympathetic over-activity, and weight gain. Furthermore, butanolic fraction prominently reduces the glucose intolerance and hyperinsulinemia in fructose-fed rats. On treatment with butanolic fraction, oxidative enzymes and the functionality of the aorta was also restored. Phytochemical analysis revealed the presence of several active constituents including bergenin, scopolin, rutinoside, kaempferol, coumaric acid, apigenin, and gingerol. In conclusion, butanolic fraction of Delphinium brunonianum has the potential to prevent and recover the fructose-induced metabolic perturbations.

Background: Citrus aurantifolia Linn. fruit, a natural dietary item, has long been used traditionally to treat hypertension in Pakistan. The current research work aims to explore the effect on blood pressure and its mechanisms., Methods: The aqueous methanol extract of plant fruit was used to evaluate hypotensive/antihypertensive, vasorelaxation, and safety profiles. Moreover, the in vitro inhibitory effect of AMECA on phosphodiesterase was also evaluated., Results: In hypotensive studies, extracts of Citrus aurantifolia fruit exhibited a concentration-dependent reduction in SBP, DBP, MAP, and heart rate. A similar effect has been observed on anesthetized rats, but the effects exerted by the extract were not altered significantly in the presence of L-NAME, atropine, captopril, and propranolol. Moreover, in coronary arteries, the extract significantly potentiated relaxations induced by cGMP- and cAMP-dependent relaxing agonists. When exposed to PDEs, the extract concentration dependently subdued cGMP-hydrolyzing activity of different PDEs with IC50 values of 40-130  μ g/mL., Conclusion: It is conceivable that extracts obtained from Citrus aurantifolia fruit produced hypotensive and antihypertensive effects in rats. The extract elicited endothelium-independent vasorelaxation, possibly by acting directly on smooth muscles of the coronary artery and by increasing cGMP and cAMP via nonselective inhibition of vascular PDEs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Syed Nasir Abbas Bukhari et al.)

The pH-sensitive polymeric matrix of basil seed gum (BSG), with two different monomers, such as acrylic acid (AA) and N , N -Methylene-bis-acrylamide (MBA), was selected to use in hydrogels preparation through a free radical copolymerization technique using potassium per sulfate (KPS) as a cross linker. BSG, AA and MBA were used in multiple ratios to investigate the polymer, monomer and initiator effects on swelling properties and release pattern of captopril. Characterization of formulated hydrogels was done by FTIR, DSC/TGA, XRD and SEM techniques to confirm the stability. The hydrogels were subjected to a variety of tests, including dynamic swelling investigations, drug loading, in vitro drug release, sol-gel analyses and rheological studies. FTIR analysis confirmed that after the polymeric reaction of BSG with the AA monomer, AA chains grafted onto the backbone of BSG. The SEM micrographs illustrated an irregular, rough, and porous form of surface. Gel content was increased by increasing the contents of polymeric gum (BSG) with monomers (AA and MBA). Acidic and basic pH effects highlighted the difference between the swelling properties with BSG and AA on increasing concentration. Kinetic modelling suggested that Korsmeyer Peppas model release pattern was followed by the drug with the non-Fickian diffusion mechanism.

Mimosa pudica seed mucilage (MPM) is composed of glucuronoxylan, which is a swellable, pH-responsive and non-toxic biomaterial. Herein, we aimed to extract MPM from M. pudica seeds (MP seeds) to ascertain optimization of extraction conditions to get highest yield by response surface methodology, via Box-Behnken design (RSM-BBD). MPM was extracted from MP seeds by a hot water extraction method. The effects of four different parameters on the extraction yield of MPM were evaluated: pH of the extraction medium (1-10), seed/water contact time (1-12 h), the temperature of extraction medium (30-90 °C), and seed/water ratio (1:5-1:35 w / v ). The maximum yield of MPM obtained by Design-Expert software was 10.66% (10.66 g/100 g) at pH 7, seed/water contact time of 6 h, extraction temperature of 50 °C, and seed/water ratio of 1:20 w / v . The p values of ANOVA were found to be less than 0.0001, which indicated that the extraction yield of MPM was significantly affected by all the study parameters. The results revealed that pH and extraction temperature were the most significant factors affecting the yield of MPM. MPM in compressed tablet form showed pH-responsive on-off switching behavior at pH 7.4 and 1.2 in a reversible manner. MPM in compressed tablet form sustained the release of itopride for 16 h following a super case-II transport mechanism and zero-order release kinetics.

Ghrelin is a multifunctional gastrointestinal acylated peptide, primarily synthesized in the stomach and regulates the secretion of growth hormone and energy homeostasis. It plays a central role in modulating the diverse biological, physiological and pathological functions in vertebrates. The synthesis of ghrelin receptor ligands after the finding of growth hormone secretagogue developed from Met-enkephalin led to reveal the endogenous ligand ghrelin and the receptors. Subsequently, many peptides, small molecules and peptidomimetics focusing on the ghrelin receptor, GHS-R1a, were derived. In this review, the key features of ghrelin's structure, forms, its bio-physiological functions, pathological roles and therapeutic potential have been highlighted. A few peptidomimetics and pseudo peptide synthetic perspectives have also been discussed to make ghrelin receptor ligands, clinical trials and their success., 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 © 2022 Elsevier Masson SAS. All rights reserved.)

Dihydrouracil presents a crucial intermediate in the catabolism of uracil. The vital importance of uracil and its nucleoside, uridine, encourages scientists to synthesize novel dihydrouracils. In this paper, we present an innovative, fast, and effective method for the synthesis of dihydrouracils. Hence, under mild conditions, 3-chloroperbenzoic acid was used to cleave the carbon-sulfur bond of the Biginelli hybrids 5,6-dihydropyrimidin-4(3 H )-ones. This approach led to thirteen novel dihydrouracils synthesized in moderate-to-high yields (32-99%).

Microcrystalline cellulose (MCC) is a versatile polymer commonly employed in food, chemical, and biomedical formulations. Lagenaria siceraria (bottle gourd) fruit is consumed in many parts of the world, and its pedicle is discarded as waste. In the quest for a novel renewable source of the MCC, the present study investigates the extraction and characterization of MCC from the pedicle of Lagenaria siceraria fruits. The MCC was extracted by sequentially treating pedicles with water, alkali, bleaching (sodium chlorite), and dilute sulfuric acid (acid hydrolysis). The removal of associated impurities from pedicle fibers was confirmed by Fourier transform infrared analyses. The extracted MCC exhibited a characteristic crystalline structure of cellulose in X-ray diffraction with a 64.53% crystallinity index. The scanning electron microscopy (SEM) showed the variation in the morphology of the fibers and the formation of MCC of approximately 100 µm. The thermogravimetric analysis (TGA) indicated higher thermal stability of MCC. MCC production from biowaste (pedicle) holds potential for application as an emulsifier, stabilizer, and thickener in the chemical, pharmaceutical, and food industries.

The present study aimed to develop a stable interconnected matrix as a sustained release drug delivery material. Arabinoxylan (AX) was extracted from ispaghula husk and then crosslinked with different concentrations, i.e., 0.5, 1.0, and 1.5 g of CaCl 2 per 0.25 g of AX. The crosslinking was confirmed through Fourier transform infrared spectroscopy. The swelling capacity of crosslinked AX (CL-AX) was evaluated against buffer solutions of pH 1.2, 6.8, 7.4, and water. The swelling capacity increased from pH 1.2 to pH 7.4 and followed the second order swelling kinetics. The swelling study also revealed that CL-AX with 1.0 g CaCl 2 showed maximum swelling capacity. The swelling-deswelling (on-off switching) behavior of CL-AX was evaluated in water-ethanol, water-0.9% NaCl solution, and buffer solutions of pH 7.4-1.2 and showed responsive swelling-deswelling behavior. Scanning electron microscopy revealed a highly porous nature of CL-AX with a mesh of thin fibrous networking. Hemocompatibility studies of CL-AX revealed its non-thrombogenic and nonhemolytic attributes. The CL-AX matrix tablet prolonged the release of enalapril maleate for 24 h, and the drug release followed the zero order kinetics and super case-II transport mechanism. Therefore, CL-AX can be recognized as a stimuli responsive and hemocompatible biomaterial with sustained drug release potential.

Dual inhibition of topoisomerase (topo) II and FLT3 kinase, as in the case of C-1311, was shown to overcome the shortcomings of using topo II inhibitors solely. In the present study, we designed and synthesized two series of pyrido-dipyrimidine- and pseudo-pyrido-acridone-containing compounds. The two series were evaluated against topo II and FLT3 as well as the HL-60 promyelocytic leukemia cell line in vitro. Compounds 6, 7, and 20 showed higher potency against topo II than the standard amsacrine (AMSA), whereas compounds 19 and 20 were stronger FLT3 inhibitors than the standard DACA. Compounds 19 and 20 showed to be dual inhibitors of both enzymes. Compounds 6, 7, 19, and 20 were more potent inhibitors of the HL-60 cell line than the standard AMSA. The results of the in vitro DNA flow cytometry analysis assay and Annexin V-FITC apoptosis analysis showed that 19 and 20 induced cell cycle arrest at the G2/M phase, significantly higher total percentage of apoptosis, and late-stage apoptosis in HL-60 cell lines than AMSA. Furthermore, 19 and 20 upregulated several apoptosis biomarkers such as p53, TNFα, caspase 3/7 and increased the Bax/Bcl-2 ratio. These results showed that 19 and 20 deserve further evaluation of their antiproliferative activities, particularly in leukemia. Molecular docking studies were performed for selected compounds against topo II and FLT3 enzymes to investigate their binding patterns. Compound 19 exerted dual fitting inside the active site of both enzymes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The continuing growth of bacterial resistance makes the top challenge for the healthcare system especially in bone-infections treatment. Current estimates reveal that in 2050 the death ratio caused by bacterial infections can be higher than cancer. The aim of this study is to provide an alternative to currently available bone-infection treatments. Here we designed mesoporous hydroxyapatite nanocarriers functionalized with citrate (Ctr-mpHANCs). Amoxicillin (AMX) is used as a model drug to load in Ctr-mpHANCs, and the drug loading was more than 90% due to the porous nature of nanocarriers. Scanning electron microscopy shows the roughly spherical morphology of nanocarriers, and the DLS study showed the approximate size of 92 nm. The Brunauer-Emmett-Teller (BET) specific surface area and pore diameter was found to be about 182.35 m 2 /g and 4.2 nm, respectively. We noticed that almost 100% of the drug is released from the AMX loaded Ctr-mpHANCs (AMX@Ctr-mpHANCs) in a pH-dependent manner within 3 d and 5 d at pH 2.0 and 4.5, respectively. The sustained drug release behaviour was observed for 15 d at pH 7.4 and no RBCs hemolysis by AMX@Ctr-mpHANCs. The broth dilution and colony forming unit (CFU) assays were used to determine the antimicrobial potential of AMX@Ctr-mpHANCs. It was observed in both studies that AMX@Ctr-mpHANCs showed a significant reduction in the bacterial growth of S. aureus , E. coli , and P. aeruginosa as compared to Ctr-mpHANCs with no bacteria-killing. Thus, we proposed that Ctr-mpHANCs can be used as a drug carrier and a treatment option for bone infections caused by bacteria.

Combinations of polymers can improve the functional properties of microspheres to achieve desired therapeutic goals. Hence, the present study aimed to formulate Prunus armeniaca gum (PAG) and sodium alginate microsphere for sustained drug release. Blended and coated microspheres were prepared using the ionotropic gelation technique. The effect of polymer concentration variation was studied on the structural and functional properties of formulated microspheres. FTIR, XRD, and thermal analysis were performed to characterize the microspheres. All the formulations were well-formed spherical beads having an average diameter from 579.23 ± 07.09 to 657.67 ± 08.74 μm. Microspheres entrapped drugs within the range 65.86 ± 0.26-83.74 ± 0.79%. The pH-dependent swelling index of coated formulations was higher than blended. FTIR spectra confirmed the presence of characteristic peaks of entrapped Tramadol hydrochloride showing no drug-polymer interaction. In vitro drug release profile showed sustained release following the Korsmeyer-Peppas kinetic model with an R 2 value of 0.9803-0.9966. An acute toxicology study employing the oral route in Swiss albino mice showed no signs of toxicity. It can be inferred from these results that blending PAG with sodium alginate can enhance the stability of alginate microspheres and improve its drug release profile by prolonging the release time.

Objectives: Polygnum hydropiper L (Polygonaceae) is commonly known as smart weed. This study was designed to assess the effect of aqueous methanolic extract of P. hydropiper on oxidative stress and metabolic changes in fructose-induced hypertensive rats., Methods: Male Sprague-Dawely rats were divided into six groups of five animals each (n = 5) and designated as normotensive group with distilled water, fructose-fed group with 10% fructose, standard control group with 10% fructose plus amlodipine (10 mg/kg) and treated groups with different doses of the aqueous methanolic extract of P. hydropiper (100, 200 and 400 mg/kg) plus 10% fructose daily for 6 weeks. Body weight gain was checked every week. Blood pressure parameters [systolic (SBP), diastolic (DBP), mean arterial pressure (MAP) and heart rate (HR)] and reactivity of extract with phenylephrine and adrenaline were measured by invasive method. Metabolic changes and oxidative stress parameters were measured from blood samples. Phytochemical analysis was also performed., Key Findings: Aqueous methanolic extract of P. hydropiper at 400 mg/kg decreased the blood pressure, heart rate, body weight and produced significant effect on metabolic and oxidative stress changes as compared to fructose-fed group. Phytochemical analysis revealed the presence of polyphenols and flavonoids in it., Conclusion: The present results showed that aqueous methanolic extract of P. hydropiper possesses effect on oxidative stress and metabolic changes due to polyphenols and flavonoids., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

New furan-based derivatives have been, designed, synthesized, and evaluated for their cytotoxic and tubulin polymerization inhibitory activities. DNA flow cytometric study of pyridine carbohydrazide 4 and N -phenyl triazinone 7 demonstrated G 2 /M phase cell cycle disruptions. Accumulation of cells in the pre-G1 phase and positive annexin V/PI staining, which may be caused by degeneration or fragmentation of the genetic components, suggested that cell death occurs via an apoptotic cascade. Furthermore, compounds 4 and 7 had a strong pro-apoptotic impact through inducing the intrinsic mitochondrial mechanism of apoptosis. This mechanistic route was verified by an ELISA experiment that indicated a considerable rise in the levels of p53 and Bax and a drop in the level of Bcl-2 when compared with the control.

A key issue with modern cancer treatments is the emergence of resistance to conventional chemotherapy and molecularly targeted medicines. Cancer nanotherapeutics were created in order to overcome the inherent limitations of traditional chemotherapeutics. Over the last few decades, cancer nanotherapeutics provided unparalleled opportunities to understand and overcome drug resistance through clinical assessment of rationally designed nanoparticulate delivery systems. In this context, various design strategies such as passive targeting, active targeting, nano-drug, and multimodal nano-drug combination therapy provided effective cancer treatment. Even though cancer nanotherapy has made great technological progress, tumor biology complexity and heterogeneity and a lack of comprehensive knowledge of nano-bio interactions remain important roadblocks to future clinical translation and commercialization. The current developments and advancements in cancer nanotherapeutics employing a wide variety of nanomaterial-based platforms to overcome cancer treatment resistance are discussed in this article. There is also a review of various nanotherapeutics-based approaches to cancer therapy, including targeting strategies for the tumor microenvironment and its components, advanced delivery systems for specific targeting of cancer stem cells (CSC), as well as exosomes for delivery strategies, and an update on clinical trials. Finally, challenges and the future perspective of the cancer nanotherapeutics to reverse cancer drug resistance are discussed.

Complex illnesses, such as cancer, are often caused by many disorders, gene mutations, or pathways. Biological pathways play a significant part in the development of these diseases. Multi-target directed ligands (MTDLs) have been used by medicinal chemists recently in an effort to find single molecules that can affect many targets concurrently. In this work, several chalcones containing the ligustrazine moiety were synthesized and tested for their in vitro anticancer activity and several cancer markers, including EGFR, BRAF V600E , c-Met, and tubulin polymerization, in order to uncover multitarget bioactive compounds. In assays using multiple cancer cell lines, the majority of the compounds examined showed strong anticancer activity against them. To synthesize oximes, all of the chalcones were used as precursors. The IC 50 values of two compounds (11g and 11e) were found to be 0.87, 0.28, 2.43, 1.04 μM and 11d, 1.47, 0.79, 3.8, 1.63 μM respectively, against A-375, MCF-7, HT-29 and H-460 cell lines. These IC 50 values revealed an excellent antiproliferative activity compared to those of the positive control foretinib, (IC 50 = 1.9, 1.15, 3.97, and 2.86 μM). Careful examination of their structure and configuration revealed that both compounds had an oxime functional group with z configuration, in place of carbonyl functional group, along with a 2-phenyl thiophenyl moiety with or without a bromo group at position-5. The possible binding pattern was implied by docking simulation, inferring the possibility of introducing interactions with the nearby tubulin chain. Since the novel structural trial has been conducted with a detailed structure activity relationship discussion, this work might stimulate new ideas in further modification of multitarget anti-cancer agents and therapeutic approaches., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Highly flexible and stretchable sensors are becoming increasingly widespread due to their versatile applicability in human/robot monitoring sensors. Conductive polymeric composites have been regarded as potential candidates for such sensors, and carbon nanotubes (CNTs) are widely used to fabricate such composites. In the present study, CNT-embedded high flexible sensors were fabricated using a facile three-roll milling method, which mitigates the drawbacks of the conventional fabrication methods. CNTs content varied between 0.5 and 4.0 wt.%, and the percolation threshold range was obtained via conductivity/resistivity values of the fabricated sensors. Following this, the electrical stability of the sensors was examined against the various DC and AC signals. Furthermore, the fabricated sensors were stretched up to 500% strain, and their sensitivity against varying strain amplitudes was investigated in terms of the change in resistance and gauge factors. Lastly, the fabricated sensors were applied to human fingers for monitoring finger bending and releasing motions to validate their potential applications. The experimental results indicated that these sensors have a percolation threshold of around 2% CNTs content, and the sensors fabricated with 2 to 4% CNTs content showed measurable resistance changes against the applied strain amplitudes of 50-500%. Among these sensors, the sensor with 2% CNTs content showed the highest sensitivity in the studied strain range, exhibiting a resistance change and gauge factor of about 90% and 1.79 against 50% strain amplitude and about 18,500% and 37.07 against 500% strain amplitude, respectively. All these sensors also showed high sensitivity for finger motion detection, showing a resistance change of between 22 and 69%.

Dietary polyphenols encompass a diverse range of secondary metabolites found in nature, such as fruits, vegetables, herbal teas, wine, and cocoa products, etc. Structurally, they are either derivatives or isomers of phenol acid, isoflavonoids and possess hidden health promoting characteristics, such as antioxidative, anti-aging, anti-cancerous and many more. The use of such polyphenols in combating the neuropathological war raging in this generation is currently a hotly debated topic. Lately, Alzheimer's disease (AD) is emerging as the most common neuropathological disease, destroying the livelihoods of millions in one way or another. Any therapeutic intervention to curtail its advancement in the generation to come has been in vain to date. Using dietary polyphenols to construct the barricade around it is going to be an effective strategy, taking into account their hidden potential to counter multifactorial events taking place under such pathology. Besides their strong antioxidant properties, naturally occurring polyphenols are reported to have neuroprotective effects by modulating the Aβ biogenesis pathway in Alzheimer's disease. Thus, in this review, I am focusing on unlocking the hidden secrets of dietary polyphenols and their mechanistic advantages to fight the war with AD and related pathology.