Synthesis of New 1, 3, 4-Oxadiazole-Incorporated 1, 2, 3-Triazole Moieties as Potential Anticancer Agents Targeting Thymidylate Synthase and Their Docking Studies.

Thymidylate synthase (TS) has emerged as a hot spot in cancer treatment, as it is directly involved in DNA synthesis. In the present article, nine hybrids containing 1,2,3-triazole and 1,3,4-oxadiazole moieties (6-14) were synthesized and evaluated for anticancer and in vitro thymidylate synthase activities. According to in silico pharmacokinetic studies, the synthesized hybrids exhibited good drug likeness properties and bioavailability. The cytotoxicity results indicated that compounds 12 and 13 exhibited remarkable inhibition on the tested Michigan Cancer Foundation (MCF-7) and Human colorectal Carcinoma (HCT-116) cell lines. Compound 12 showed four-fold inhibition to a standard drug, 5-fluoruracil, and comparable inhibition to tamoxifen, whereas compound 13 exerted five-fold activity of tamoxifen and 24-fold activity of 5-fluorouracil for MCF-7 cells. Compounds 12 and 13 inhibited thymidylate synthase enzyme, with an half maximal inhibitory concentration, IC50 of 2.52 µM and 4.38 µM, while a standard drug, pemetrexed, showed IC50 = 6.75 µM. The molecular docking data of compounds 12 and 13 were found to be in support of biological activities data. In conclusion, hybrids (12 and 13) may inhibit thymidylate synthase enzyme, which could play a significant role as a chemotherapeutic agent.

Synthesis and suggestion of a new nanometric gold(III) melatonin drug complex: an interesting model for testicular protection.

AIM: Melatonin (MLT) is a major hormone secreted by the pineal gland. In this study, a gold(III) MLT (Au+3/MLT) complex has been synthesized and investigating its protective effects against testicular damage. METHODOLOGY: The structural features of the complex were investigated. For biological assessment, 30 male rats were divided into three groups for 30 days. The first control group, the second received MLT and the third received Au+3/MLT complex. RESULTS: The Au+3/MLT complex was found to be nonelectrolytic with formula (Au[MLT]2[Cl][H2O]). The ligand is monodentate and adopt square-planar geometry. Its particles range in diameter from 35 to 100 nm. MLT affords slight oxidative stress protection. The Au+3/MLT complex significantly decreases TNF-α and IL-1ß levels but elevates antioxidant enzyme capacities, reducing lipid peroxidation markers and improving testicular histological structure. CONCLUSION: The Au+3/MLT complex improves the anti-inflammatory actions of MLT, exhibits potent antioxidant activity and enhances reproductive capacity.