Comprehensive drug-like assessment of pyridine carbothioamide analogs: from molecular modeling to in-vivo evaluation

To evaluate the anti-inflammatory potential of novel class of chemical compounds designed by the linkage of carbothioamide moiety with pyridine. In silico analysis was conducted using molecular docking followed by an in vitro cytotoxicity assay and evaluation of anti-inflammatory activity. Subsequently, in vivo performance was determined using the Complete Freund’s Adjuvant-induced inflammatory model, employing macroscopic, histopathological, and protein expression analyses. Molecular interaction studies revealed that compound R2 displayed the most favorable binding mode with human nitric oxide synthase, cyclooxygenase-1, and cycloxygenase-2. All compounds exhibit dose-dependent cytotoxicity. Notably, compound R4 was safer at higher concentration, whereas compound R2 was comparatively toxic. The in vitro anti-inflammatory activity demonstrated half maximal inhibitory concentration (IC50) values ranging from 10.25 ± 0.0 to 23.15 ± 4.24 µM, with compound R6 exhibiting the lowest IC50 value and compound R3 showing the highest. The in vivo results corroborated the anti-inflammatory effects, with a significant reduction in paw size (p The study highlights the promise of discovering new anti-inflammatory drugs containing pyridine moiety with proven potency, efficacy, and reduced side effects.