Synthesis and biological properties of the seven alanine‐modified analogues of the marine cyclopeptide hymenamide C

Abstract

The synthesis and biological activity of the marine cyclopeptide hymenamide C(1), showing an inhibitory effect on human neutrophil elastase degranulation release, were recently described. Based on this result, it was decided to undertake a systematic structure-activity relationship study of this cyclopeptide, based on the Ala-scan technique, in order to obtain useful information for the rational design of additional analogues. The synthesis and characterization of the seven Ala modified analogues are reported and their biological and pharmacological properties are described.

Marine pharmacology in 2001–2002: Marine compounds with anthelmintic, antibacterial, anticoagulant, antidiabetic, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems and other miscellaneous mechanisms of action

“…Although hymenamide C inhibition of human neutrophil degranulation (IC 50 =18 μM) was not particularly impressive, the authors noted that cyclosporine, a clinically used immunosuppressive cyclopeptide, exerted "weaker inhibitory effect on elastase release". A structure-activity relationship study completed with this cyclopeptide concluded a "non-receptorial mode of action" for hymenamide C and its synthetic analogs (Napolitano et al, 2002). Dal Piaz et al (2002) reported an extensive investigation of the mechanism of phospholipase A 2 (PLA 2 ) inactivation by the novel marine sesterterpene petrosaspongiolide M (60), a bioactive sesterterpene isolated from the marine sponge Petrosaspongia nigra.…”