Computational and Molecular Docking Studies of New Benzene Sulfonamide
Drugs with Anticancer and Antioxidant Effects
Authors: Mohamed Hussein S. , Abdelgawad Mohamed A. , Hegab Momtaz , Hamza Zeinab S. , Nagdy Amany M. , Ahmed Sayed A. , Ahmed Osama M. , Ghoneim Mohammed M. 
Published: October 2022

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.