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

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 ( 1 H & 13 C 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 i n-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 IC 50 value of 16 ​μM and 3b with an IC 50 value of 11 ​μM possessed maximum cytotoxic activity against the AGS cell line in comparison to the reference, Oxaliplatin (IC 50 ​= ​29 ​μM). • We designed and synthesized a small library of eighteen novel 1,2,3-triazole clubbed hybrids of aurones. • Hybrids 3o , 3p , and 3r possessed potent inhibition towards cathepsin B with % inhibition of the range 83.05-87.16%. • In-vitro cathepsin B inhibitory study was also supported by the in-silico drug modeling studies. • Hybrids 3a , 3b , and 3e exhibited remarkable activity against AGS cell line with IC 50 values 11-21 μM .