Synthesis and Bioactivity of a Cyclopolypeptide from Caribbean Marine Sponge

Synthesis of a natural proline-rich cyclopolypeptide rolloamide A was carried out by coupling of triand tetrapeptide units Boc-Phe-Pro-Val-OMe and Boc-Pro-Leu-Pro-Ile-OMe after proper deprotection at carboxyl and amino terminals using carbodiimide chemistry in alkaline environment followed by cyclization of linear heptapeptide segment in the presence of base. The structure of synthesized peptide was confirmed by spectral techniques including FTIR, H-1 NMR, C-13 NMR, MS analyses. Newly synthesized peptide was subjected to biological screening against pathogenic microbes and earthworms. Cyclopeptide 8 possessed promising activity against pathogenic fungi Candida albicans (ZOI: 24 mm, MIC: 6 mu g/mL) and Gram-negative bacteria Pseudomonas aeruginosa (ZOI: 27 mm, MIC: 6 mu g/mL) and Klebsiella pneumoniae (ZOI: 23 mm, MIC: 12.5 mu g/mL), in comparison to reference drugs - griseofulvin (ZOI: 20 mm, MIC: 6 mu g/mL) and ciprofloxacin (ZOI: 25 mm, MIC: 6 mu g/mL/ZOI: 20 mm, MIC: 12.5 mu g/mL). Also, newly synthesized heptacyclopeptide exhibited potent anthelmintic activity against earthworms Megascoplex konkanensis, Pontoscotex corethruses, and Eudrilus species (MPT/MDT ratio - 8.22-16.02/10.06-17.59 min), in comparison to standard drugs mebendazole (MPT/MDT ratio - 10.52-18.02/12.57-19.49 min) and piperazine citrate (MPT/MDT ratio - 12.38-19.17/13.4422.17 min).