Design, synthesis, anticancer activity of new amide derivatives derived from 1,2,3-triazole-benzofuran hybrids: An insights from molecular docking, molecular dynamics simulation and DFT studies

A new series of amide derivatives derived from 1,2,3-triazole-benzofuran hybrids (9a-j) have been syn-thesized and their structures were confirmed by using spectroscopic/analytical techniques. All the syn-thesized compounds were evaluated for their anticancer activity in four human cancer cell lines i.e.; PC3 (Prostate cancer), A549 (Lung cancer), MCF7 (Breast cancer), and A2780 (Ovarian cancer) by employ-ing MTT assay using etoposide as the reference compound. In comparison to etoposide, all of the com-pounds showed good to moderate activity. The IC50 values of the novelamide derivatives (9a-j) ranged -from 0.013 +/- 0.0012 mu Mto 21.8 +/- 8.52 mu Mwhereas positive control (etoposide) showed1.38 +/- 0.56 mu M to 3.08 +/- 0.135 mu M respectively. The developed amide derivatives of 1,2,3-triazole-benzofuran hybrids were found to be good alternative anticancer agents. Among the new amide derivatives (9a-j), mainly 9a-c, 9i, and 9j displayed highly potent anticancer activity towards MCF7 (9a, 9j), A549(9b), A2780(9c) and PC3(9i) human cancer cell lines respectively. Furthermore, using molecular docking simulations with the BCL-2 (PDB ID: 4LVT), Colchicine binding site of Tubulin (PDB ID: 1SA0), Kinase domain of C-ABL (PDB ID: 1IEP) and CLK-2 (PDB ID: 6FYL) proteins, the experimentally observed biological impact of new amide derivatives (9a-j) were investigated, and it was discovered that our experimental findings are consistent with the computationally derived results. Molecular docking predictions were further supported by MD simulation and DFT studies. The docking scores of the newly produced amide derivatives (9a-j) varied from-2.74 kcal/mol to-8.022 kcal/mol, indicating increased inhibitory actions. Human oral absorption is expected to be greater than 70%. (c) 2022 Elsevier B.V. All rights reserved.