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

Aim: To evaluate the anti-inflammatory potential of novel class of chemical compounds designed by the linkage of carbothioamide moiety with pyridine.

Materials & methods: 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.

Results: 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 < 0.001). Among the tested compounds, compound R4 exhibited the most potent anti-inflammatory activity, whereas R2 exhibited the least potency.

Conclusion: The study highlights the promise of discovering new anti-inflammatory drugs containing pyridine moiety with proven potency, efficacy, and reduced side effects.