1,2,3-triazole clubbed and dichloro substituted novel aurones as potential anticancer agents targeting digestive enzymes: Design, synthesis, DFT, ADME and molecular docking studies

In the present investigation, we engineered some 1,2,3-triazole clubbed and dichloro substituted novel aurones as potential anticancer agents well capable of targeting digestive enzymes. These novel 2-(2,6-dichlorobenzylidene)-6-((1-aryl-1H-1,2,3-triazol-4-yl)methoxy)benzofuran-3(2H)-one derivatives or 1,2,3-triazoleaurone based hybrid molecules, were initially designed, synthesized, and thoroughly characterized and later studied for their impact on AGS cancer cell line and digestive enzymes. Some remarkable outcomes were observed in the anticancer screening of these compounds as almost all aurone-triazole hybrids (eighteen among ninteen) were found to exhibit IC50 values, lower (IC50= 7.73-30.69 mu M) than the reference drug leucovorin (IC50= 30.8 mu M), except for hybrid 10k (IC50= 67.03 mu M). Also in the in-vitro screening, against three digestive enzymes, most of these hybrid compounds, exhibited some significant activity. Notably, compound 10l exhibited substantial activation of lipase (% activation = 175.8 +/- 4.1), compound 10n displayed inhibition against alpha-amylase (% inhibition = 36.7 +/- 1.3), and compound 10i produced inhibition against trypsin (% inhibition = 65.7 +/- 2.0). Additionally, in-silico molecular docking was utilized to evaluate interactions between proteins and ligands, unveiling binding patterns of the novel synthesised compounds and the reference drug with the receptor proteins. Assessing therapeutic potential, an in-silico ADMET model demonstrated that the synthesized molecules possess favorable drug-like properties. The hybrids underwent computational scrutiny employing the DFT/ B3LYP method, encompassing the determination of Frontier Molecular Orbital energy values, along with the calculation of diverse quantum chemical parameters.