Abstract

Synthesis, molecular docking study, and cytotoxic activity of a new group of 1,3,5-triaryl pyrazole derivatives were be studied. The antiproliferative activity of the final compounds were 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 and doxorubicin were evaluated as positive controls. All compounds demonstrated cytotoxic activity in mentioned cell lines, in a dose dependent manner. Among all, compounds (5j, 5b, and 5d) showed the highest cytotoxicity in some cancerous cell lines with IC₅₀ less than 5.0 μM. In addition, compound 5g, one of the most potent compounds, showed an interestingly low cytotoxic effect on NIH3T3 cell line, which is a noncancerous cell line. 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 synthesis of their new derivatives.

In molecular modeling, study all synthesized compounds were docked in the colchicine-binding site of tubulin α and β chains and the predicted binding energy was calculated. Our data indicate that these derivatives may present promising chemotherapeutic agents, possibly targeting microtubules.

Keywords: 1, 3, 5-Triaryl pyrazoles, anticancer, cytotoxicity, molecular docking, tubulin.

Graphical Abstract