Structural Analysis of a New Cytotoxic Demethylated Analogue of Neo-N-methylsansalvamide with a Different Peptide Sequence Produced by Fusarium solani Isolated from Potato

Abstract

A novel cytotoxic cyclic pentadepsipeptide, neosansalvamide, was produced by Fusarium solani KCCM90040 isolated from Fusarium-contaminated potato in Korea. The molecular formula of neosansalvamide was analyzed as C32H50N4O6 by electrospray ionization tandem mass spectrometry and combined structural analysis. The one- and two-dimensional nuclear magnetic resonance and absolute configuration of amino acid spectral data allowed for the resolution of cyclic five subunits linked in the following order: (S)-leucic acid, two L-leucine, L-valine, and L-phenylalanine, and this sequence shows a molecular structure as a new demethylated analogue of neo-N-methylsansalvamide but having a different peptide sequence. The cytotoxic effects of neosansalvamide were investigated by sulforhodamine B bioassay on four human cancer cell lines. The IC50 value of neosansalvamide required to inhibit cell growth in vitro by 50% for A549 (lung cancer), SK-OV-3 (ovarian cancer), SK-MEL-2 (skin melanoma), and MES-SA (uterine sarcoma) cell lines were 11.70 +/- 0.55, 10.38 +/- 0.64, 13.99 +/- 1.32, and 11.75 +/- 0.13 mu M, respectively (mean +/- standard error).