Synthesis, anticancer evaluation, photophysical properties and molecular docking studies of new thiazolyl-thiadiazolyl ketones (D-π-A structured)

Abstract

A series of thiazolyl-thiadiazolyl ketones 5a and 5b and their corresponding Schiff’s bases 6a and 6b were synthesized based on the reaction of 2-(2-amino-4-methylthiazol-5-yl)-N-(4-nitrophenyl)-2-oxoacetohydrazonoyl bromide (3) with two types of 2-substituted-3-mercapto-3-(phenylamino)acrylonitrile compounds 4a and 4b. The presence of two potent electron-withdrawing nitrile groups on one side and N,N-dimethylaminobenzylidene moiety on the other side of the thiazolyl-thiadiazolyl ketone 6a promoted maximum UV–Vis absorption. Meanwhile, an in vitro MTT cytotoxicity assay was applied to investigate the activity of the synthesized thiazolyl-thiadiazolyl ketones 5a, 5b, 6a, and 6b on four different cell lines: HepG2, VoLo, MCF-7, and WI38. The cytotoxic possessions were compared to those of the drug reference (Dox). The outcomes revealed varying efficacy towards cancer cell lines, exhibiting cytotoxic selectivity for VoLo and MCF-7. The cytotoxic effectiveness of the thiazolyl-thiadiazolyl ketones revealed good effectiveness, with IC50 values ranging from 11.29 to 22.13 µM. Moreover, the SAR investigation of thiazolyl-thiadiazolyl ketones helped to clarify the reason for their powerful cytotoxic effectiveness. The molecular docking stimulation for the synthesized thiazolyl-thiadiazolyl ketones was looked at against the PDB: 5YJB protein to explore how they bind.