Triazole based novel molecules as potential therapeutic agents: Synthesis, characterization, biological evaluation, in-silico ADME profiling and molecular docking studies

In this study, eight new compounds (7a-h) based on triazole compounds containing ester groups were synthe-sized with high yields. The structures of the synthesized compounds (7a-h) were elucidated by various spec-troscopic methods (element analysis, FT-IR, 1H-(13C) NMR). Antioxidant, anticancer, and alpha-amylase enzyme inhibition activities of synthesized new triazole derivatives were carried out, and the effects of different groups on the activity were investigated. When the determined antioxidant properties of the compounds were examined, all synthesized compounds showed a moderate radical scavenging effect against radicals depending on the concentration (6.25-200 g/mL). All compounds except the three derivatives were found to have higher IC50 values than the standard drug acarbose (IC50: 891 mu g/mL) according to the alpha-amylase enzyme inhibition results. Compound 7g (IC50: 50 g/mL) was discovered to have nearly eighteen (18) times the activity of the conventional medication acarbose (IC50: 891 mu g/mL). Compounds synthesized for anticancer activity studies were screened against the Hela cell line, and the results were compared with standard cis-platinum (IC50: 16.30 mu g/mL). Compound 7g (IC50: 19.78 mu g/mL) was found to have almost the same activity as cis-platinum. Using Qikprop, the compounds were thoroughly tested for ADME qualities, and none violated any drug similarity standards. According to ADME data, whole physicochemical drug-likeness parameters of molecules remained within defined ranges as stipulated in the Lipinski rules (RO5) and revealed a high bioavailability profile. The molecular docking results with 2QV4 and 4GQR alpha-amylase enzymes demonstrated that all molecules have a high af-finity, indicating polar and apolar interaction with critical amino acids in the alpha-amylase binding pocket.

Journal

CHEMICO-BIOLOGICAL INTERACTIONS

Year

2023

Volume

370

ISSN

0009-2797

eISSN

1872-7786

DOI

10.1016/j.cbi.2022.110312

WoS UID

WOS:000973479700001