Journal
FRONTIERS IN PHARMACOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.958379
Keywords
saccharinyl hydrazide; DFT; docking; POM analyses; pharmacophore sites; MD
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Funding
- Taif University Researchers [TURSP-2020/91]
- Taif University, Taif, Saudi Arabia
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Saccharine is an active scaffold with pharmacological significance for various biological activities. In this study, saccharinyl hydrazine was synthesized and transformed into a key precursor for a series of small molecules with different moieties. The compounds exhibited strong antibacterial and anticancer activities, with 6c and 10a being the most active analogs. Theoretical calculations and molecular docking studies provided insights into the potential mechanisms of action for these compounds.
Saccharine is a pharmacologically significant active scaffold for various biological activities, including antibacterial and anticancer activities. Herein, saccharinyl hydrazide (1) was synthesized and converted into 2-[(2Z)-2-(1,1-dioxo-1,2-dihydro-3H-1 lambda(6),2- benzothiazole-3-ylidene) hydrazinyl] acetohydrazide (5), 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 Staphylococcus and Escherichia coli , and the results indicated that compounds 6c and 10a were the most active analogs with an inhibition zone diameter of 30-35 mm . In cell-based anticancer assay over Ovcar-3 and M-14 cell lines, compound 10a was the most potent analog with IC50 values of 7.64 & PLUSMN; 0.01 and 8.66 & PLUSMN; 0.01 mu M, 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.
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