First Total Synthesis and Biological Screening of a Proline-Rich Cyclopeptide from a Caribbean Marine Sponge

Abstract

A natural heptacyclopeptide, stylissamide G (<b>7</b>), previously isolated from the Bahamian marine sponge <i>Stylissa caribica</i> from the Caribbean Sea, was synthesized via coupling of the tetrapeptide l-phenylalanyl-l-prolyl-l-phenylalanyl-l-proline methyl ester with the tripeptide Boc-l-leucyl-l-isoleucyl-l-proline, followed by cyclization of the linear heptapeptide fragment. The structure of the synthesized cyclooligopeptide was confirmed using quantitative elemental analysis, FT-IR, ¹H NMR, ¹³C NMR and mass spectrometry. Results of pharmacological activity studies indicated that the newly synthesized cycloheptapeptide displayed good anthelmintic potential against <i>Megascoplex konkanensis</i>, <i>Pontoscotex corethruses</i> and <i>Eudrilus eugeniea</i> at 2 mg/mL and in addition, potent antifungal activity against pathogenic <i>Candida albicans</i> and dermatophytes <i>Trichophyton mentagrophytes</i> and <i>Microsporum audouinii</i> at a concentration of 6 μg/mL.