Novel 1,2,3-triazole-aurone hybrids as cathepsin B inhibitors: One-pot synthesis, anti-proliferative, and drug modeling studies

Abstract

In the present study, we have designed a series of novel 1,2,3-triazole-aurone hybrids, which were synthesized by a one-pot click reaction between a terminal alkyne and an in-situ generated azide, and evaluated as potential cathepsin B inhibitors. The structures of the synthesized compounds were confirmed by various spectroscopic techniques (1H & 13C NMR and HRMS data). The in-vitro cathepsin B inhibitory study of the synthesized compounds showed that the hybrids named 3o, 3p, and 3r are the excellent inhibitors with percentage inhibition of 83.05–87.16% at the concentration of 10−5 ​M, in comparison to standards, Aspirin (48.21% at 10−7 ​M), and Curcumin (52.27% at 10−7 ​M). The docking study was also in support of the in-vitro assay. Furthermore, the anti-proliferative impact of these synthesized compounds was also evaluated against the gastric adenocarcinoma cell line (AGS cell line). The in-vitro MTT assay suggested that out of all the synthesized hybrids, compounds 3a with an IC50 value of 16 ​μM and 3b with an IC50 value of 11 ​μM possessed maximum cytotoxic activity against the AGS cell line in comparison to the reference, Oxaliplatin (IC50 ​= ​29 ​μM).

Keywords

• Aurones
• Anti-proliferative activity
• Cathepsin B inhibitors
• One-pot synthesis
• 1,2,3-Triazole