Novel 1,2,4-triazoles as anti-enzymatic agents: Microwave versus conventional synthesis, characterization, docking and BSA binding studies

Abstract

In the drug development process, 1,2,4-triazoles have become widely acknowledged as an effective structural motif. Through both classical and microwave supported approaches, analogues based on 1,2,4-triazole were synthesized, and they have the potential to act as strong anti-enzymatic agents. Starting from 4‑methoxy benzensulfonyl chloride (1), subsequent carboxylate (3), carbohydrazide (4), 1,2,4-triazole (5) and their hybrids,7a-j, were successfully synthesized in attractive yields. All the synthesized analogs were characterized by 1H NMR, 13CNMR and IR spectral data. The enzymes acetyl cholinesterase (AChE), butyryl cholinesterase (BChE), and lipoxygenase (LOX), which are in charge of a variety of problems in people's daily lives, were considered in the biological assessment. Compounds,7g(IC50 (µM)=3.15±0.13) and 7h(IC50 (µM)=3.48±0.11) were outstanding against AChE while compounds, 7g(IC50 (µM)=39.17±0.29) and 7j(IC50 (µM)=35.42±0.41)against BChE comparative to Eserine(IC50 (µM)=0.19±0.05, 0.62±0.08)used as a standard respectively against both enzymes respectively. Inhibition potential against LOX was found excellent by compounds 7a(IC50 (µM)=12.53±0.25) and 7j(IC50 (µM)=19.28±0.46) among all the tested compoundsrelative to Quercetin(IC50 (µM)=2.34±0.35) used as a standard. The molecular docking and BSA (bovine serum albumin) binding studies further supported the physiologically active anti-enzymatic behaviors of synthesized compounds and they could be the future anti-enzymatic drugs after further assessments.