A series of novel 4-amino-5-substituted-1,2,4-triazole-3-thiol derivatives (B1-B18) were synthesized and characterized by spectral analysis. Equimolar portions of thiocarbohydrazide and different acids (substituted aryl/heteroaryl/aliphatic) were fused to synthesize the title compounds. The compounds were evaluated for cytotoxicity, in vitro anti-inflammatory activity and antioxidant activities. Cytotoxicity studies highlighted B4 (2,4-dichloro analog) as the potent cytotoxic molecule with IC50 value of 20.35 μM against MCF-7 cell line compared to cisplatin (IC50 = 12.06 μM). B4 (2,4-dichloro), B18 (oleayl) and B14 (2-hydroxy) showed significant membrane-stabilizing activity with IC50 values < 35 μM, whereas B11 (3,4-dimethoxy), B4 (2,4-dichloro) and B14 (2-hydroxy) displayed moderate proteinase inhibitory activity with IC50 values < 72 μM. Compounds possessing phenolic hydroxyl group (B12−B14) demonstrated an appreciable antioxidant activity in the studied antioxidant models. QSAR analysis revealed the important contribution of molecular connectivity, ionization potential and mass of the compounds for optimum cytotoxicity. Present results suggested compound B4 as a potential lead molecule to design novel and potent cytotoxic and anti-inflammatory agents.

Background: Cancer is the world's leading cause of death; more than ten million people die from cancer each year. Rate of morbidity and mortality is increasing day by day. As a result, utilizing chemoinformatics techniques, a novel series of Methylenedioxyphenyl linked with 3,4,5-trimethoxyphenyl/ 2,5-dimethoxyphenyl and pyrimidine has been designed, docked and in-silico predictions of pharmacokinetic, and toxicological parameters. Materials and Methods: A novel class of Methylenedioxyphenyl derivatives was docked by using AutoDock Vina software to reveal the interaction of these derivatives with the active site topoisomerase-II with PBD ID 5GWK. In addition to the above, the ADME studies were performed using Swiss ADME software and the toxicity parameters using the pkCSM online tool. Results: Many derivatives were found to be more active than the standard drug etoposide in docking studies. Binding interaction pattern of selected compounds were studied with the active sites of DNA topoisomerase-II (PBD ID 5GWK) by docking simulation. The results of the screening revealed that compounds B9, B12, B13, B15, B16, B17, B18, B22, and B23 were more active candidates of the series. Conclusion: Molecular docking and ADME/Tox properties of new methylenedioxyphenyl derivatives have been described. As a result, nine compounds from the intended series showed improved docking scores with suitable ADME/Tox properties and satisfactory topo II inhibiting activity, thus these compounds may be the effective inhibitors of topoisomerase IIα enzyme.

A series of novel phenoxy acetyl carboxamides (4a-4g) were synthesized by amidation using phenoxy acetyl hydrazide and various acid chlorides (benzoyl, adamantly carbonyl cinnamoyl, 4-chloro benzoyl chlorides) or bases (piperidine, morpholine & substituted piperidinone) and evaluated for antioxidant and antinociceptive activities. The title compounds were purified by recrystallization using ethanol and characterized by spectral (FTIR, 1H NMR, and Mass) analysis. Compound 4a was effective in scavenging the DPPH radicals (57%) and nitric oxide (NO) radicals (52%) while compound 4e was able to significantly neutralize ABTS cation radicals (58%). However, the radical scavenging ability was lesser compared to the standard antioxidant agents. Among the tested compounds, 4f and 4g elicited good antinociceptive activity in the central and peripheral animal models (25 mg/kg body weight). Compounds 4b and 4f seem to open ATP-sensitive potassium channels (KATP channels), a possible mechanism for their peripheral effects. The carboxamides bind well with the monoglyceride lipase enzyme (MAGL) and established strong interactions at the active site.