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

Abstract

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-1λ6,2- 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 ± 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.

New Anthranilic Acid Hydrazones as Fenamate Isosteres: Synthesis, Characterization, Molecular Docking, Dynamics & in Silico ADME, in Vitro Anti‐Inflammatory and Anticancer Activity Studies

“…The high‐resolution 3D crystal structures of proteins were obtained from the Protein data bank. 1PXX was used for COX‐II, [32] 5QIN was used for TGF‐βII [33] and 3 W2S was used for EGFR [34] . The XP docking scores of selected compounds were given in Table 3.…”

“…1PXX was used for COX-II, [32] 5QIN was used for TGF-βII [33] and 3 W2S was used for EGFR. [34] The XP docking scores of selected compounds were given in Table 3.…”

Modulating Ionic Linkages in the Heterocyclic Sulfated Polysaccharide Carrageenan for Enhanced Selectivity Against Amelanotic Melanoma Cells

“…In addition to the invitro cell line assay the mechanism through the literature, gene mapping, and in-silico studies were also done to support the study. [54] To calculate the IC 50 value the concentration and % inhibition plot through prizm software with the non-linear regression method using variable slop with four parameter with best fit values like the bottom Top, Hill slope, Span, through the calculation of R 2 value, which shows significance of the slop with best fit line. The value close to 1 is high significant and best fit model with the least error in the predicated and actual value.…”

“…The relative resistance was established as IC 50 cell line/IC 50 sensitive parent cell line. The in-vitro cytotoxicity assay protocol were adopted as per the refernces [32,54] Cell Viability…”

Molecular Modeling and Synthesis of Indoline-2,3-dione-Based Benzene Sulfonamide Derivatives and Their Inhibitory Activity against α-Glucosidase and α-Amylase Enzymes

“…This estimation has become a standard step in designing new drug compounds. Herein, the Preadmet server ( 32 ) and admetSAR server ( 23 ) were utilized to predict the drug-likeness, pharmacokinetics properties, and toxicity of the benzenesulfonohydrazide derivatives.…”