Evaluation of the anti-inflammatory and anti-nociceptive activities of novel synthesized melatonin analogues

A straightforward and efficient synthesis of novel melatonin analogues containing fused pyrrole or pyridine nucleus was investigated. The pyrrolo[1,2-a]indole derivatives 3, 5, 12, 14 and pyrido[1,2-a]indole derivatives 9a, b were synthesized and their structures were established based on the analytical and spectral data. The potential role of the novel synthesized melatonin analogues 3, 5, 9a and 12 as anti-inflammatory and anti-nociceptive agents in comparison with melatonin was studied. Compound 5 has the strongest anti-inflammatory activity which exceeds that of the parent reference, melatonin, followed by compounds 9a and 12, at the first 2 h of administration. Effects of melatonin analogues 3, 5, 9a and 12 on thermal pain, acetic acid-induced writhing and gastric lesions caused by indomethacin were also investigated in comparison with melatonin. Compounds 5 and 12 were more potent as anti-nociceptive drugs; they are more potent in this respect than melatonin.