Structure-Based Rationale Design and Synthesis of Aurantiamide Acetate Analogues - Towards a New Class of Potent Analgesic and Anti-inflammatory Agents

• Published in: Chemical biology & drug design Vol. 79; no. 5; pp. 850 - 862
• Main Authors: Suhas, Ramesh, Channe Gowda, Dase
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2012; Wiley
• Subjects: analgesics; Analgesics - chemical synthesis; Analgesics - chemistry; Analgesics - pharmacology; Analgesics - therapeutic use; Animals; anti-inflammatory agents; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; aurantiamide acetate; Biochemistry & Molecular Biology; Carrageenan; Chemistry, Medicinal; Dipeptides - chemical synthesis; Dipeptides - chemistry; Dipeptides - pharmacology; Dipeptides - therapeutic use; Drug Design; Edema - chemically induced; Edema - drug therapy; elastin-based peptides; Female; Life Sciences & Biomedicine; Male; Mice; Pain - drug therapy; Pharmacology & Pharmacy; Polygonum - chemistry; Rats; Science & Technology; synthesis; Ulcer - chemically induced; synthesis; SERIES; RAT; elastin-based peptides; ELASTIN MESSENGER-RNA; ALZHEIMERS-DISEASE; AMINO-ACIDS; DRUGS; analgesics; anti-inflammatory agents; aurantiamide acetate; AGONIST
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/j.1747-0285.2012.01331.x

A series of new aurantiamide acetate analogues were synthesized by modifying its N‐terminal substitution and the amino acid residue. The structure of all these compounds was established on the basis of analytical and spectral studies. All the new derivatives were evaluated in vivo for their analgesic activity by tail flick method in mice and anti‐inflammatory activity against carrageenan‐induced oedema in albino rats at different doses (25, 50 and 100 mg/kg body weight). All the compounds exhibited significant pharmacological activity with no ulcerogenic liability. In particular, pentapeptides and tricosamers (30 amino acids) containing analogues have demonstrated high potency than the reference standards. These compounds hold promise for further development. The present work reports the synthesis and characterization of a new class of aurantiamide acetate analogues as potent analgesic and anti‐inflammatory agents with no ulcerogenic liability.