Discovery of new 1,4-disubstituted 1,2,3-triazoles: <i>in silico</i> ADME profiling, molecular docking and biological evaluation studies

Abstract

In this work, eight new 1,2,3-triazoles (<b>6a-h</b>) were synthesized from acetylenes' "click" reaction with <i>p</i>-substituted azide derivatives. The structures of the compounds were characterized using standard analytical and spectroscopic methods (elemental analysis, FT-IR, ¹H(¹³C)NMR). The anticancer, antioxidant, α-amylase, ADME, molecular docking studies of synthesized triazoles were investigated. According to α -amylase enzyme inhibition results, all compounds except <b>6c</b> (IC₅₀: 2299 μg/mL) were found to have a higher IC₅₀ value than the standard drug acarbose (IC₅₀: 891 μg/mL). Compound <b>6g</b> (IC₅₀: 68 μg/mL) exhibited 13 times higher activity than standard acarbose. All compounds, except <b>6e</b>, have been shown to have greater DPPH radical scavenging capabilities than BHT and β-carotene standards. According to ABTS radical scavenging studies, all compounds showed higher scavenging activity than ascorbic acid and Trolox. To determine the anticancer activity of the synthesized compounds, they were screened against the Hela cell line, and the results were compared with standard cisplatin (IC₅₀: 16.30 μg/mL). Compound <b>6a</b> (IC₅₀: 49.03 μg/mL) was determined to have moderate activity relative to cisplatin. The compounds were examined comprehensively for ADME characteristics and did not violate any drug-likeness rule. ADME data showed that all physicochemical and pharmacological parameters of the compounds remained within defined limits as specified in Lipinski's rules (RO5) and put forth a high bioavailability profile. The molecular docking findings show that all molecules have a high affinity by exhibiting polar and apolar contact with essential residues in the binding pocket of α-amylase.Communicated by Ramaswamy H. Sarma.