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

Abstract

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. 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. 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. 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. 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.