Ultrasound assisted a one pot multicomponent and greener synthesis of 1,2,3-triazole incorporated aurone hybrids: Cathepsin B inhibition, anti-cancer activity against AGS cell line, and in-silico docking evaluation

Cathepsin B represents a group of lysosomal-encapsulated cellular cysteine proteases, whose upregulation is the critical risk factor for cancer progression and in the regulation of degenerative processes like apoptosis. Therefore, cysteine cathepsins are used as effective biomarkers for cancers and other neurodegenerative disorders and have become specific targets in drug designing. To diversify the pharmacological potential of aurones, a total of eighteen novel 1,2,3-triazole decorated aurone hybrids were synthesized in very good yields, utilizing click chemistry and an ultrasound-assisted one-pot, multicomponent and greener protocol, straight from hydroxy-substituted aurones. These hybrids have been evaluated as useful cathepsin B inhibitors and further explored their in-vitro study over AGS cell line using MTT assay. The in-vitro cathepsin B inhibitory potential of the synthesized hybrids revealed that the hybrid 3p possesses a very significant inhibition (% inhibition ​= ​85.02) at the concentration of 10 −6 M compared to the standard aspirin (% inhibition ​= ​48.21 ​at 10 −7 M) and curcumin (% inhibition ​= ​57.72 ​at 10 −7 M), which further supported by the in-silico studies. In addition to this, the cytotoxic assay of the hybrids showed that the hybrids 3d (IC 50 ​= ​24 ​μM), 3i (IC 50 ≈ 24 ​μM), and 3m (IC 50 ​= ​26 ​μM) exhibit comparable anti-tumor activity against AGS cell line than the standard, oxaliplatin (IC 50 ​= ​29 ​μM). The results suggested that the reported novel aurone-1,2,3-triazole hybrids are a promising candidate for the development of new cathepsin B inhibitors as well as anti-cancer leads. • US-promoted aqueous media domino synthesis of eighteen novel 1,2,3-triazole incorporated aurone hybrids. • Hybrids 3p displayed good inhibition towards cathepsin B with % inhibition of 85.02% at micromolar range . • In-silico drug modeling studies supports the in-vitro cathepsin B inhibitory evaluation. • Hybrids 3d (IC 50 =24 ​μM) and 3i (IC 50 =24 ​μM) exhibited significant activity against AGS cell line, compared to the standard Oxaliplatin (29 ​μM).