Total Synthesis and Biological Potential of Psammosilenin A

Abstract

The present work reports the synthesis of a plant-originated cyclooctapeptide--psammosilenin A 8--by cyclization of linear peptide fragment phe-pro-phe-phe-ala-pro-leu-pro-Opfp which was prepared by coupling of tetrapeptide units Boc-phe-pro-phe-phe-OH and ala-pro-leu-pro-OMe followed by proper deprotection of terminal groups and activation of the acid functionality. During synthesis, dicyclohexylcarbodiimide (DCC) and N,N-diisopropylcarbodiimide (DIPC) were used as the coupling agents and N-methylmorpholine (NMM)/triethylamine (TEA) were used as bases. Structure of the synthesized peptide was elucidated by spectral as well as elemental data. The newly synthesized peptide was subjected to biological screening and found to possess potent cytotoxic activity against DLA and EAC cell lines with IC(50) value of 7.93 and 17.06 microM, respectively. Furthermore, good anthelmintic activity against earthworms M. konkanensis and Eudrilus species at 1 and 2 mg/mL was also observed for the synthesized cyclic peptide. Studies indicated that N-methylmorpholine was a more useful base for cyclization of linear peptide unit in comparison to pyridine.