Design, Synthesis, And Evaluation Of Novel 1,3,4-OxadiazoleLinked Benzothiazole Hybrids As Dual-Acting COX Inhibitors And Central Analgesic Agents

Abstract

Inflammation and pain remain interconnected physiological responses in numerous chronic disorders, often necessitating combination therapies. The present study reports the design, synthesis, and pharmacological evaluation of a new series of 1,3,4-oxadiazole-linked benzothiazole hybrids aimed at dual inhibition of cyclooxygenase (COX) isoforms and central analgesic pathways. The rationale was built upon the known anti-inflammatory potential of the 1,3,4-oxadiazole nucleus and the analgesic relevance of benzothiazole scaffolds. A multi-step synthetic scheme involving condensation, cyclization, and amide coupling reactions was employed to generate the target compounds (Vt1–Vt12), which were structurally confirmed through FTIR, ¹H-NMR, and mass spectral analysis. The anti-inflammatory activity was assessed using carrageenan-induced paw edema in rats, while central analgesic efficacy was evaluated by Eddy’s hot plate method. Notably, compound Vt8 exhibited significant COX inhibition and anti-inflammatory activity, while compound Vt11 demonstrated potent central analgesic effects. Structure–activity relationship (SAR) analysis revealed the critical influence of lipophilic and electron-donating substituents on biological activity. The findings establish these molecular hybrids as promising dual-action agents for future anti-inflammatory and pain-relief therapies.