Synthesis, Molecular Docking Study, and Cytotoxic Activity of 3,4-diaryl-5-(4-pyridinyl)-1,2,4-oxadiazole

Background: Triaryl oxadiazoles have been proven to be useful agents against various types of cancer cell lines. Nevertheless, their mechanism of action is not fully understood. Objective: Synthesis and cytotoxic activity of a new group of triaryl oxadiazoles; 3,4-diaryl-5-(4- pyridinyl)-1,2,4-oxadiazole derivatives, will be discussed in this study. Their cytotoxic activity has been examined in 4 different cell lines by MTT method. Method: 3,4-Diaryl-5-(4-pyridinyl)-1,2,4-oxadiazole derivatives were prepared from condensation of different imines with 4-substituted benzohydroxyiminoyl chlorides. The antiproliferative activity of the final compounds was examined in MCF-7, AGS, HT-29 and NIH3T3 cell lines by MTT assay, using different concentrations of each compound to determine their IC50. The cytotoxic activity of paclitaxel, doxorubicin and combretastatin A-4 was evaluated as positive controls. Results: All compounds demonstrated cytotoxic activity in mentioned cell lines, in a dose dependent manner. Among all, 6d-2 showed the highest cytotoxicity in AGS and MCF-7 cell lines with IC50 19.84 and 9.91 respectively and 6c-2 was the most potent in HT-29 with IC50 27.60. In addition, 6c-1, one of the most potent compounds, showed an interestingly low cytotoxic effect on NIH3T3 cell line, which is a noncancerous cell line. In the molecular modeling study, all compounds had comparable binding energy in Colchicine binding site and 6c-2 had the best-predicted binding energy. Conclusion: Together, our data suggest that the synthesized compounds have a partially selective mechanism of action against cancer cells and possibly a lower toxic effect on normal cells, making them interesting candidates for the synthesis of new anticancer agents.