Article

First total synthesis and biological screening of hymenamide E

Department of Pharmaceutical Chemistry, Rajiv Academy for Pharmacy, Mathura-281 001, India.
Acta Pharmaceutica (Impact Factor: 0.91). 12/2006; 56(4):399-415.
Source: PubMed

ABSTRACT

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.

Download full-text

Full-text

Available from: Rajiv Dahiya
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Plant-originated cyclopolypeptide (XIII) was synthesized by coupling of dipeptide Boc-l-asn(bzh)-l-phe-OH and tetrapeptide gly-l-leu-l-ala-l-tyr-OMe followed by cyclization of a linear hexapeptide segment. Structure elucidation of XIII was done on basis of detailed spectral analysis including FTIR, 1H NMR, 13C NMR, FAB MS and elemental analysis. From the results of pharmacological screening, it was concluded that XIII possesses high cytotoxic activity against DLA and EAC cell lines with CTC50 values of 15.1 μM and 18.6 μM, and potent antimicrobial activity against pathogenic fungi C. albicans with MIC of 6 μg mL−1. Moreover, XIII possesses moderate anthelmintic activity against earthworms M. konkanensis, P. corethruses, and Eudrilus sp. at 2 mg mL−1 dose level.
    Full-text · Article · Oct 2008 · Chemical Papers- Slovak Academy of Sciences
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The synthesis of a natural cyclic peptide cherimolacyclopeptide E (12) by coupling of tripeptide units Boc-gly-leu-gly-OCH3 (9) and Boc-phe-tyr-pro-OCH3 (10) after proper deprotection at carboxyl and amino terminals followed by cyclization of linear hexapeptide segment, is described. Structure elucidation of the cyclopeptide 12 is based on detailed spectral analysis such as FTIR, 1H NMR, 13C NMR, FAB MS and elemental analysis. After biological screening, the newly synthesized peptide exhibited high cytotoxicity against Dalton’s lymphoma ascites (DLA) and Ehrlich’s ascites carcinoma (EAC) cell lines with CTC50 values of 2.76 and 4.96 μM, and potent antimicrobial activity against pathogenic microbes P. aeruginosa, E.coli and C. albicans with MICs between 12.5-6 μg/mL. Furthermore, compound 12 possessed moderate anthelmintic activity against earthworms M. konkanensis, P. corethruses and Eudrilus sp. at 2 mg/mL dose level.
    Preview · Article · Sep 2007 · Journal of the Chilean Chemical Society
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Present investigation describes the synthesis of a natural phenylalanine-rich cyclopolypeptide longicalycinin A (10) by coupling of dipeptide unit Boc-L-phe-L-tyr-OH with tripeptide unit L-pro-L-phe-gly-OMe followed by cyclization of linear segment. Synthesized cyclic pentapeptide was characterized by spectral techniques including FTIR, 1H/13C NMR, FAB MS and elemental analysis and screened for different pharmacological activities. It was found that it has good anthelmintic activity against Megascoplex konkanensis, Pontoscotex corethruses and Eudrilus sp. at 2 mg/ml concentration, in addition to high cytotoxicity against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines with CTC50 values of 2.62 and 6.37 microM. Dermatophytes were found to be moderately sensitive towards newly synthesized peptide.
    Full-text · Article · Nov 2007 · Pakistan journal of pharmaceutical sciences
Show more