[Cytotoxic activity of two cyclic peptides from the latex of Jatropha integerrima Euphorbiaceae].

Abstract

Activity-guided fractionation of the ethyl acetate extract of the latex of Jatropha integerrima Euphorbiaceae combinated with cytotoxic assay against the KB human nasopharyngeal carcinoma cells, resulted to the isolation by chromatographic methods including HPLC of two new cyclopeptides: integerrimacyclopeptide4 and integerrima cyclopeptide B. The amino acid composition was established after hydrolysis and derivatization. All chiral amino acids were L configuration and were hydrophobic. Their sequences were determined by MS fragmentations (ESI-q-TOF, MS/MS) and confirmed by 2D NMR homo- and heteronuclear studies. Integerrimacyclopeptide A was a cyclooctapeptide with m/z 766 corresponding to the molecular formula C37H66N8O9. Analysis of mass spectra gave b(n) and a(n) acylium ion series which the sequence could be deduced: cyclo(Leu-Gly-Ser-Ile-Ile-Leu-Gly-lle). This structure was confirmed by interpretation of HMBC and ROESY spectra. Likewise, integerrimacyclopeptide B was a cycloheptapeptide with m/z 651 and C31H53N7O8 as molecular formula containing one proline residue: cyclo(Pro-Gly-Thr-Ile-Gly-Ile-Leu). These two cyclic peptides exhibited significant cytotoxic activityin vitro against KB tumorales cells with respective IC50 values of 0.46 +/- 0.04 and 0.66 +/-0.08 microg/ml.