Sulfonamide derivatives mediate breast and lung cancer cell line killing through tubulin inhibition

Abstract

Tubulin plays essential roles in cell signaling, division, proliferation, and other cellular functions. Tubulin is a potential target for anticancer agents. The classical tubulin inhibitors have a low therapeutic index, multi-drug resistance, and induced tubulin gene mutations. Therefore, the discovery of alternative tubulin inhibitors is critical for cancer therapy. The study aimed to synthesize sulfonamide derivatives to combat breast and lung cancer by tubulin inhibition mediated mechanism. In the present work sulfonamide derivatives were synthesized and physicochemically characterized in terms of melting points, magnetic measurements, IR,1H NMR, 13C NMR, thermogravimetric analysis, and molecular weights. Moreover, the cytotoxicity and western blot analysis were investigated using MCF7, and A549 cell lines as surrogate models for breast and lung cancer. The present results showed that the modified sulfonamides agents elicited cytotoxicity against breast cancer cell line MCF7 as well as A549 cell lines with IC50 values below 1.8 µM. Among the designed sulfonamide derivatives the 4-iodo-N-(3-((2-methyl-5-(trifluoromethyl) benzyl) oxy)-4-(N-methylmethylsulfonami-do) phenyl) benzamide is the most effective cytotoxic agent against MCF7 and A549 cell lines. These data demonstrated that sulfonamide agents have excellent anti-cancer activity targeting tubulin in both cancer cell lines.