DESIGN, SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF NOVEL HETEROCYCLIC COMPOUNDS

Inflammation is a protective biological response; however, its chronic manifestation is closely associated with the development of several pathological conditions. The limitations and adverse effects of existing anti-inflammatory drugs necessitate the search for safer and more effective alternatives. In the present study, a series of novel heterocyclic derivatives of 2-thiouracil were designed, synthesized, and evaluated for their in-vitro anti-inflammatory activity. Twelve Schiff base derivatives (6a–6l) were synthesized through sulfonylation, hydrazinyl substitution, and subsequent condensation with various substituted aromatic aldehydes. The synthesized compounds were characterized by melting point determination, elemental analysis, and physicochemical evaluation. In-vitro anti-inflammatory activity was assessed using inhibition of albumin denaturation and human red blood cell (HRBC) membrane stabilization assays, with aspirin serving as the reference standard. All tested compounds exhibited concentration-dependent anti-inflammatory activity. Among them, derivatives 6h and 6b demonstrated the most significant inhibition of protein denaturation and superior membrane stabilization activity, approaching the efficacy of aspirin at higher concentrations. Structure–activity relationship analysis suggested that electron-donating substituents and halogen substitution patterns play a crucial role in enhancing biological activity. These findings indicate that 2-thiouracil-based heterocyclic derivatives represent promising lead compounds for the development of novel anti-inflammatory agents, warranting further in-vivo and mechanistic studies.