PARALLEL SYNTHESIS AND ANTI-INFLAMMATORY ACTIVITY OF CYCLIC PEPTIDES CYCLOSQUAMOSIN D AND ITS ANALOGS
Afef Dellai, Igor Maricic, Vipin Kumar, Abderrahman Bouraoui, Adel Nefzi
Unite de Recherche URSAM, faculté de pharmacie, avenue Avicenne, 5000 Monastir, Tunisie
Cyclic peptides constitute an important group of natural product compounds. Naturally occurring cyclic peptides continue to hold the attention of synthetic chemists and biologists alike for their intriguing chemical structures and potent biological activities. Recently, cyclic peptides cyclosquamosin D (A1) has been isolated from seeds of Annona squamosa and was reported to have an anti-inflammatory activity.
We report the parallel synthesis of this natural cyclopeptide (A1) and its analogs. All of the compounds were screened for anti-inflammatory activity by evaluating their inhibitory effects on the production of pro-inflammatory cytokines using the lipopolysaccharide stimulated macrophage J774A.1 cell line. Compounds having significant anti-inflammatory activity in suppressing the secretion of IL-6 and TNF-α have been identified, some of which exhibit activity superior to that observed with the natural products.