Antinociceptive activity of thymoquinone and its structural analogues: A structure-activity relationship study.

Abstract

Purpose: To investigate the structural features that influence the antinociceptive activity of thymoquinone and their structural analogues. Methods: The quinones were prepared by an oxidation procedure using molecular oxygen and catalysis with [CoII(salen)] from the respective phenols. The antinociceptive activity of para-benzoquinones (10 mg/kg, ip) was evaluated using formalin test in mice. Vehicle (5 % Tween 80) or morphine (10 mg/kg) were used as control group and standard drug, respectively. The amount of time spent licking the injected paw was considered as the nociceptive response. Results: Among the compounds tested, five para-benzoquinones showed antinociceptive activity. The 2-isopropyl-para-benzoquinone presented the highest potency in first and second phases and produced a near-maximal inhibition (p < 0.001) in the formalin test, similar to morphine (p < 0.001). Conclusion: Our experimental results show that by appropriate structural modification of parabenzoquinones it may be possible to develop novel analgesic drugs.