Acta Pharm. 56 (2006) 399-415

full paper

Original research paper

First total synthesis and biological screening of hymenamide E

Rajiv Dahiya¹*, devender pathak¹, MALIPEDDI Himaja² and Sunita Bhatt¹

rajivdahiya77@rediffmail.com

¹Department of Pharmaceutical Chemistry, Rajiv Academy for Pharmacy, Mathura-281 001, India

²NGSM Institute of Pharmaceutical Sciences, Nanthoor, Mangalore-575 005, India

Accepted July 27, 2006

A new potent bioactive, proline-rich cyclic heptapeptide hymenamide E (13) was synthesized using the solution phase technique by cyclization of the linear peptide Boc-Phe-Pro-Thr-Thr-Pro-Tyr-Phe-OMe (12) after proper deprotection at carboxyl and amino terminals. Linear peptide segment was prepared by coupling the tripeptide unit Boc-Phe-Pro-Thr-OH (10a) with the tetrapeptide unit Thr-Pro-Tyr-Phe-OMe (11a) using dicyclohexylcarbodiimide as the coupling agent and N-methylmorpholine as the base. Structures of all new compounds were characterized by IR, ¹H NMR spectral data as well as elemental analyses. In addition, the structure of compound 13 was verified by ¹³C NMR, fast atom bombardment mass spectroscopy and differential scanning calorimetry. The newly synthesized cyclopeptide was screened for its antibacterial, antifungal and anthelmintic activities against eight pathogenic microbes and two earthworm species. Compound 13 showed potent antifungal activity against Candida albicans and Ganoderma species comparable to that of griseofulvin as a reference drug and potent anthelmintic activity against earthworms Megascoplex konkanensis and Eudrilus species in comparison to piperazine citrate.

Keywords: hymenamide E, cyclic heptapeptide, antibacterial activity, antifungal activity, anthelmintic activity