Synthesis, molecular docking study, and anticancer activity of triaryl-1,2,4-oxadiazole

This study describes synthesis of a new group of triaryl-1,2,4-oxadiazole derivatives and their anticancer activities. The target compounds were prepared from reaction of different imines and 4-substituted benzohydroxyiminoyl chlorides. All the synthesized compounds were screened for antiproliferative activities against MCF7 and K562 cell lines using MTT assay at 50-mu M concentration. Four compounds that showed more than 50 % cytotoxicity were selected for determination of IC50. Out of these, 6c-1y showed remarkable inhibitory cytotoxicity activity against MCF7 and K562 cell lines with IC50 6.50 and 21.66 mu M, respectively. A molecular modeling study where 6c-1y was docked in the binding site of COX-2 showed a 2.3- hydrogen bond forming via hydroxyl group of Ser516 residue and oxygen of central oxadiazole ring and triaryl moiety of 6c-1y oriented toward the hydrophobic pockets of COX-2. Our data indicate that these derivatives may present promising chemotherapeutic agents, possibly targeting COX-2 pathway.