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In the current study, we report the synthesis of novel 4-((1-((1 H -1,2,3-triazole-4-yl)methyl)-1 H -indol-3-yl)methylene)-5-methyl-2-phenyl-2,4-dihydro-3 H -pyrazole-3-one derivatives 5a - o . The compounds were prepared through a Knoevenagel condensation reaction and copper-catalyzed azide-alkyne cycloaddition (CuAAC) Click chemistry approach. The synthesized compounds exhibited promising antimicrobial activity against both Gram-positive and Gram-negative bacteria. Compounds 5e , 5h , and 5i displayed potent activity with MIC value 10 μg/mL against Acinetobacter baumannii , in comparison to standard drugs chloramphenicol and ampicillin. Compounds 5d , 5h , 5i , 5l , 5m, and 5n exhibited good-to-moderate antifungal activity against Candida albicans and Aspergillus niger equivalent to standard drugs nystatin and fluconazole. In this study, the cytotoxicity profile of a series of compounds was assessed using SHSY-5Y cells. The results indicate that compounds 5a - o exhibit no significant cytotoxicity at concentrations up to 100 μg/mL , in comparison to both untreated and vehicle control groups. These findings highlight the safety and tolerability of compounds as well as the potential of the synthesized compounds as effective agents against bacterial and fungal infections., Competing Interests: The authors declare no competing financial interest., (© 2025 The Authors. Published by American Chemical Society.)

In this study, we describe a one-pot three-component synthesis of bioactive tetrahydopyrimidinecarboxamide derivatives employing lanthanum triflate as a catalyst. Out of the synthesized compounds, 4f had the most potent anti-cancer activity and impeded cell cycle progression effectively. Anti-cancer bioactivity was observed in 4f against liver, breast, and lung cancers as well as primary patient-derived glioblastoma cell lines. Compound 4f effectively inhibited the 3D neurosphere formation in primary patient-derived glioma stem cells. Specifically, 4f exhibited synergistic cytotoxicity with the EGFR inhibitor that is the clinical epidermal growth factor receptor inhibitor osimertinib. 4f does not exhibit anti-kinase activity and is cytostatic in nature, and further work is needed to understand the true molecular target of 4f and its derivatives. Through our current work, we establish a promising tetrahydopyrimidinecarboxamide-based lead compound with anti-cancer activity, which may exhibit potent anti-cancer activity in combination with specific clinically relevant small molecule kinase inhibitors., Competing Interests: DBU, JN, RMV, SB, and HMP are named inventors on the patent no. 528662 awarded by the government of India on 18th March 2024 pertaining to these reported compounds. No other conflicts of interest reported., (This journal is © The Royal Society of Chemistry.)

There is a continuous and pressing need to establish new brain-penetrant bioactive compounds with anti-cancer properties. To this end, a new series of 4'-((4-substituted-4,5-dihydro-1H-1,2,3-triazol-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile (OTBN-1,2,3-triazole) derivatives were synthesized by click chemistry. The series of bioactive compounds were designed and synthesized from diverse alkynes and N 3 -OTBN, using copper (II) acetate monohydrate in aqueous dimethylformamide at room temperature. Besides being highly cost-effective and significantly reducing synthesis, the reaction yielded 91-98 % of the target products without the need of any additional steps or chromatographic techniques. Two analogues exhibit promising anti-cancer biological activities. Analogue 4l shows highly specific cytostatic activity against lung cancer cells, while analogue 4k exhibits pan-cancer anti-growth activity. A kinase screen suggests compound 4k has single-digit micromolar activity against kinase STK33. High STK33 RNA expression correlates strongly with poorer patient outcomes in both adult and pediatric glioma. Compound 4k potently inhibits cell proliferation, invasion, and 3D neurosphere formation in primary patient-derived glioma cell lines. The observed anti-cancer activity is enhanced in combination with specific clinically relevant small molecule inhibitors. Herein we establish a novel biochemical kinase inhibitory function for click-chemistry-derived OTBN-1,2,3-triazole analogues and further report their anti-cancer activity in vitro for the first time., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

In the face of escalating challenges of microbial resistance strains, this study describes the design and synthesis of 5-({1-[(1H-1,2,3-triazol-4-yl)methyl]-1H-indol-3-yl}methylene)thiazolidine-2,4-dione derivatives, which have demonstrated significant antimicrobial properties. Compared with the minimum inhibitory concentrations (MIC) values of ciprofloxacin on the respective strains, compounds 5a, 5d, 5g, 5l, and 5m exhibited potent antibacterial activity with MIC values ranging from 16 to 25 µM. Almost all the synthesized compounds showed lower MIC compared to standards against vancomycin-resistant enterococcus and methicillin-resistant Staphylococcus aureus strains. Additionally, the majority of the synthesized compounds demonstrated remarkable antifungal activity, against Candida albicans and Aspergillus niger, as compared to nystatin, griseofulvin, and fluconazole. Furthermore, the majority of compounds exhibited notable inhibitory effects against the Plasmodium falciparum strain, having IC 50 values ranging from 1.31 to 2.79 μM as compared to standard quinine (2.71 μM). Cytotoxicity evaluation of compounds 5a-q on SHSY-5Y cells at up to 100 μg/mL showed no adverse effects. Comparison with control groups highlights their noncytotoxic characteristics. Molecular docking confirmed compound binding to target active sites, with stable protein-ligand complexes displaying drug-like molecules. Molecular dynamics simulations revealed dynamic stability and interactions. Rigorous tests and molecular modeling unveil the effectiveness of the compounds against drug-resistant microbes, providing hope for new antimicrobial compounds with potential safety., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Owing to the massive importance of dihydropyrimidine (DHPMs) scaffolds in the pharmaceutical industry and other areas, we developed an effective and sustainable one-pot reaction protocol for the synthesis of ( R / S )-2-thioxo-DHPM-5-carboxanilides via the Biginelli-type cyclo-condensation reaction of aryl aldehydes, thiourea and various acetoacetanilide derivatives in ethanol at 100 °C. In this protocol, taurine was used as a green and reusable bio-organic catalyst. Twenty-three novel derivatives of ( R / S )-TDHPM-5-carboxanilides and their structures were confirmed by various spectroscopy techniques. The aforementioned compounds were synthesized via the formation of one asymmetric centre, one new C-C bond, and two new C-N bonds in the final product. All the newly synthesized compounds were obtained in their racemic form with up to 99% yield. In addition, the separation of the racemic mixture of all the newly synthesized compounds was carried out by chiral HPLC (Prep LC), which provided up to 99.99% purity. The absolute configuration of all the enantiomerically pure isomers was determined using a circular dichroism study and validated by a computational approach. With up to 99% yield of 4d, this one-pot synthetic approach can also be useful for large-scale industrial production. One of the separated isomers (4 R )-(+)-4 S developed as a single crystal, and it was found that this crystal structure was orthorhombic., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

In this study, we effectively developed a catalyst-free multicomponent synthesis of 5-((2-aminothiazol-5-yl)(phenyl)methyl)-6-hydroxypyrimidine-2,4(1 H ,3 H )-dione derivatives employing 2-aminothiazole, N ', N '-dimethyl barbituric acid/barbituric acid and different aldehydes at 80 °C in an aqueous ethanol medium (1 : 1) using group-assisted purification (GAP) chemistry. The essential characteristics of this methodology include superior green credential parameters, metal-free multicomponent synthesis, faster reaction times, greater product yields, simple product purification without column chromatography and higher product yields. All of the synthesized compounds were analyzed against the HepG2 cell line. Compounds 4j and 4k shows good anti-proliferative effects on HepG2 cells. Furthermore, the ABTS and DPPH scavenging assays were used to determine the antioxidant activity of all compounds (4a-r). In both ABTS and DPPH radical scavenging assays, compounds 4e, 4i, 4j, 4o and 4r exhibit excellent potency compared to the standard ascorbic acid., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

An efficient, regioselective, and environmentally benign approach was established using the multicomponent reaction-based synthesis of novel antioxidant spiroquinoline derivatives such as spiro[dioxolo[4,5- g ]quinoline], spiro[dioxino[2,3- g ]quinoline], and spiro[pyrazolo[4,3- f ]quinoline] by reaction of aryl aldehyde, Meldrum's acid, and amine derivatives under an additive-free reaction in aqueous ethanol. Here, two asymmetric carbon centers, three new C-C bonds, and one C-N bond are developed in the final motif. This synthetic methodology offers excellent yields with an easy workup procedure, high diastereoselectivity [d.r. >50:1 ( cis / trans )], admirable atom economy, and low E -factor values. Synthesized spiro compounds were investigated for their in vitro antioxidant activity by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. In the ABTS radical scavenging assay, compounds 4d , 4f , and 4l exhibit excellent potency, and in the DPPH radical scavenging assay, compounds 4a , 4d , 4f , and 4g , exhibit excellent potency., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

We report a one-pot two-step synthesis of a bioactive 6-amino-2-pyridone-3,5-dicarbonitrile derivative using natural product catalysts betaine and guanidine carbonate. Anti-cancer bioactivity was observed in specific molecules within the library of 16 derivatives. Out of the compounds, 5o had the most potent anti-cancer activity against glioblastoma cells and was selected for further study. Compound 5o showed anti-cancer properties against liver, breast, lung cancers as well as primary patient-derived glioblastoma cell lines. Furthermore, 5o in combination with specific clinically relevant small molecule inhibitors induced enhanced cytotoxicity in glioblastoma cells. Through our current work, we establish a promising 6-amino-2-pyridone-3,5-dicarbonitrile based lead compound with anti-cancer activity either on its own or in combination with specific clinically relevant small molecule kinase and proteasome inhibitors., Competing Interests: The authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Herein, acetic acid mediated multicomponent synthesis of novel 2,4-dimethoxy-tetrahydropyrimido[4,5- b ]quinolin-6(7 H )-one (2,4-dimethoxy-THPQs) was reported. Single-crystal XRD analysis of four newly developed crystals of 2,4-dimethoxy-THPQs and their DFT study were also reported. The structure of all molecules was optimized using DFT B3LYP/6-31G(d) level and compared with the corresponding single-crystal XRD data. As a result, the theoretical and experimental geometrical parameters (bond lengths and bond angles) were found to be in good agreement. Frontier molecular orbital (FMO) and molecule electrostatic potential (MEP) analyses were used to investigate the physicochemical properties and relative reactivity of 2,4-dimethoxy-THPQs. The formation of strong C-H⋯O and N-H⋯O interaction was investigated by Hirshfeld analysis. Furthermore, electronic charge density concentration in 2,4-dimethoxy-THPQs was analysed by the Mulliken atomic charges which helps to predict the ability of 2,4-dimethoxy-THPQs to bind in the receptor. The molecular docking of the crystal structure of 2,4-dimethoxy-THPQs in the main protease (M pro ) of SARS-CoV-2 suggested that all four 2,4-dimethoxy-THPQs efficiently docked in M pro . Furthermore, 2,4-dimethoxy-THPQs with a 3-chloro substitution in the phenyl ring have the highest binding affinity because of the additional formation of halogen bonds and highest dipole moment., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Context: Coronary artery disease (CAD) is the blockage of coronary arteries, usually consequent to atherosclerosis. CAD is a lifestyle disease with an increasing disease burden in society. Evaluation of risk factors for CAD is crucial for its prevention. Lifestyle components like calorie consumption chronology, saturated fatty acid (SAFA) intake, reclining time, nocturnal eating and intermittent fasting were considered., Aims: To correlate calorie distribution, SAFA intake, reclining time, nocturnal eating and intermittent fasting with occurrence of CAD., Study Design/materials and Methods: A case-control study consisting of 235 cases and 185 controls. Questionnaire was self-designed according to NIN guidelines. Study was ICMR funded and data analysis was done using Microsoft Excel and IBM SPSS., Results: Across case and control groups, total calorie consumption difference was insignificant ( P = 0.42). Calories consumed in breakfast slot ( P = 0.001) and dinner slot ( P = 0.003) were significantly different possibly due to discrepancy among circadian variation in insulin sensitivity and calorie consumption distribution. Reclining time <1 h in afternoon (odds ratio [OR] = 2.24, 95%, 1.481-3.356) and night (OR = 2.05, 95% confidence limit [CL], 1.233-3.410), SAFA consumption (OR = 2.006, 95% CL, 1.214-3.316), intermittent fasting (OR = 1.748, 95% CL, 0.997-3.067) and nocturnal eating (OR = 1.291, 95% CL, 0.779--2.141) are potential risk factors., Conclusions: Calorie consumption chronology, SAFA intake, Reclining time, Nocturnal eating and intermittent fasting emerged as significant risk factors., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Community Medicine.)