AUTHOR=Abdellattif Magda H. , Elkamhawy Ahmed , Hagar Mohamed , Hadda Taibi Ben , Shehab Wesam S. , Mansy Wael , Belal Amany , Arief M. M. H. , Hussien Mostafa A. 

TITLE=Novel saccharin analogs as promising antibacterial and anticancer agents: synthesis, DFT, POM analysis, molecular docking, molecular dynamic simulations, and cell-based assay

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.958379

DOI=10.3389/fphar.2022.958379

ISSN=1663-9812

ABSTRACT=<p>Saccharine is a pharmacologically significant active scaffold for various biological activities, including antibacterial and anticancer activities. Herein, saccharinyl hydrazide (<bold>1</bold>) was synthesized and converted into 2-[(2Z)-2-(1,1-dioxo-1,2-dihydro-3H-1λ<sup>6</sup>,2- benzothiazole-3-ylidene) hydrazinyl] acetohydrazide (<bold>5</bold>), which was employed as a key precursor for synthesizing a novel series of small molecules bearing different moieties of monosaccharides, aldehydes, and anhydrides. Potent biological activities were found against <bold><italic>Staphylococcus</italic></bold> and <bold><italic>Escherichia coli</italic></bold>, and the results indicated that compounds <bold>6c</bold> and <bold>10a</bold> were the most active analogs with an inhibition zone diameter of 30–35 mm<bold><italic>.</italic></bold> In cell-based anticancer assay over Ovcar-3 and M-14 cell lines, compound <bold>10a</bold> was the most potent analog with IC<sub>50</sub> values of 7.64 ± 0.01 and 8.66 ± 0.01 µM, respectively. The Petra Orisis Molinspiration (POM) theoretical method was used to calculate the drug score of tested compounds and compare them with their experimental screening data. Theoretical DFT calculations were carried out in a gas phase in a set of B3LYP 6-311G (d,p). Molecular docking studies utilizing the MOE indicated the best binding mode with the highest energy interaction within the binding sites. The molecular docking for Ovcar-3 was carried out on the ovarian cancer protein (3W2S), while the molecular docking for M-14 melanoma was carried out on the melanoma cancer protein (2OPZ). The MD performed about 2ns simulations to validate selected compounds’ theoretical studies.</p>