Computational and Molecular Docking Studies of New Benzene Sulfonamide Drugs with Anticancer and Antioxidant Effects

Background: The studies on the potential usage of benzene sulfonamide derivatives as anticancer agents are limited. benzene sulfonamide derivatives are currently used as anticancer agents against different breast cancer cell lines, such as MCF-7, lung cancer cells (A549), prostate cancer cells (Du-145), and cervical cells (HeLa). Objective: A series of new sulfonamide drugs are synthesized by reacting aldehydes thio-semi-carbazones derivatives with benzene sulphonyl chloride to form benzylidene-N-(phenylsulfonyl) hydrazine-1-carbothioamide derivatives. Studying the anticancer effects against MCF-7 breast carcinoma cell lines and the antioxidant activities of these newly synthesized compounds. Methods: Studying the anticancer effects against MCF-7 breast carcinoma cell lines and the antioxidant activities of these newly synthesized compounds. To study the anti-breast cancer activity of the newly synthesized compounds, a molecular docking study is used to analyze the binding energy for the nonbonding interactions between the ligands (studied compounds) and receptor (4PYP (pdb code: 4FA2)) against human breast cancer (MCF-7) cells. The bioavailability of all studied compounds is confirmed by pharmacological investigations using Mol inspiration and absorption, distribution, metabolism, excretion, and toxicity online servers. Results: The two derivatives, 2-(4- methoxy benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4c) and 2-(4-dimethylamino) benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4e) show the most potent anticancer effects against MCF-7 breast carcinoma cell lines. Meanwhile, these two derivatives show the lowest antioxidant activities. Conclusion: The different spectral techniques were used to confirm the structure of the novel synthesized compounds. Further, 2-(4-(dimethyl amino) benzylidene)-N- (phenylsulfonyl)hydrazine-1-carbothioamide (4e) and 2-(4- methoxy benzylidene)-N-(phenylsulfonyl) hydrazine-1 carbothioamide (4c) were the most potent anticancer derivatives against MCF-7 breast carcinoma cell lines. Furthermore, they exhibited the most potent antioxidant activities. Meanwhile, the 2-benzylidene-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4a) and 2-(4-chloro benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4d) had the lowest antioxidant potentials. The estimated binding energies, inhibition constant, intermolecular energies, and reference RMSD produced from docking for all studied compounds were reported. These values showed that all studied compounds formed stable complexes with the receptor with high binding affinity. It was further noted from the ADMET analysis that compounds 4c, 4d, and 4e have good absorption, low toxicity in the human liver, and medium BBB penetration. Hence, these studied compounds (4c-4e) may be suggested as potential compounds against human breast cancer MCF-7 cells.