Synthesis, Photophysical Properties, and Molecular Docking Studies of New Nitropyridine Linked 4-Arylidene-thiazolidin-4-ones (D-π-A Structured) as Potent Anticancer Agents

Abstract

The newly synthesized 5-arylidine-2-((5-nitropyridin-2-yl)imino)thiazolidin-4-ones 4a–4d were established in a good yield by Knoevenagel type of condensation with four diverse benzaldehyde derivatives branched with electron-donating moieties by refluxing in acetic acid . Meanwhile, investigate the photophysical properties of freshly synthesized conjugates 4a–4d, with an emphasis on their behavior in various solvents. Furthermore, differences in absorbance maxima among solvents indicated varying degrees of conjugation and electrical interactions within the molecules. Moreover, the cytotoxicity assessments demonstrated that, although these hybrids are typically less powerful than the conventional drug 5-Fu, they show extraordinary selectivity against certain cancer types. Notably, conjugate 4b showed strong activity against MCF-7 cells with an IC₅₀ of 6.41 ± 0.21 μM, while conjugate 4d was very effective in HepG2 cells with an IC₅₀ of 7.63 ± 0.05 μM. Molecular docking experiments confirmed these results by demonstrating effective interactions with the active region of the chosen protein. Given its promising pharmacokinetic profile, which includes intermediate solubility, good gastrointestinal absorption, and compliance with Lipinski's rule of five, conjugate 4d emerged as the most viable option for continued drug development.