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

This study aimed at evaluation of the reactivity of melatonin ( 1) towards various chemical reagents to produce new melatonin analogues containing heterocyclic moieties which would provide basic pharmacological activities. The pyrrolo[1,2- a]indole derivatives 3, 5, 12, 14 and pyrido[1,2- a]indole d...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2007-10, Vol.42 (10), p.1285-1292
Main Authors: Elmegeed, Gamal A., Baiuomy, Ayman R., Abdel-Salam, Omar M.E.
Format: Article
Language:English
Subjects:
Analgesics
Analgesics, Non-Narcotic - chemical synthesis
Analgesics, Non-Narcotic - chemistry
Analgesics, Non-Narcotic - therapeutic use
Animals
Anti-inflammatory
Anti-Inflammatory Agents - chemical synthesis
Anti-Inflammatory Agents - chemistry
Anti-Inflammatory Agents - therapeutic use
Anti-nociceptive
Biological and medical sciences
Bones, joints and connective tissue. Antiinflammatory agents
Edema - drug therapy
Edema - pathology
Extremities
Indole
Medical sciences
Melatonin
Melatonin - analogs & derivatives
Melatonin - chemical synthesis
Melatonin - chemistry
Melatonin - therapeutic use
Mice
Molecular Structure
Neuropharmacology
Pharmacology. Drug treatments
Pyridine
Pyrrole
Rats
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Summary:This study aimed at evaluation of the reactivity of melatonin ( 1) towards various chemical reagents to produce new melatonin analogues containing heterocyclic moieties which would provide basic pharmacological activities. The pyrrolo[1,2- a]indole derivatives 3, 5, 12, 14 and pyrido[1,2- a]indole derivatives 9a, b were synthesized via straightforward and efficient methods and their structures were established based on the analytical and spectral data. Also, this work was extended to study 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. After s.c. administration all compounds induced significant anti-inflammatory activity, inhibiting the paw oedema response compared with the control group at all time points in the test. 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. Effect of melatonin analogues on thermal pain, acetic acid-induced writhing and gastric lesions caused by indomethacin was also investigated. Compounds 5 and 12 were more potent as anti-nociceptive drugs; they are more potent in this respect than melatonin. 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. [Display omitted]
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2007.01.027