Cytotoxic Peptaibols from Trichoderma strigosum

Five new lipopeptaibols (1-5) and eight new 19-residue peptaibols (8-15) along with two known lipopeptaibols, lipovelutibols C (6) and D (7) were isolated from Trichoderma strigosum. The planar structures of the newly discovered peptaibols (1-5, 8-15) were elucidated using 1D and 2D NMR, and UPLC-MS/MS data. The absolute configurations for new peptaibols (1-5, 8-15) were elucidated using the advanced Marfey's method and GITC (2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl isothiocyanate) derivatization. Through analysis of CD spectra, these peptabols were found to have right-handed helical conformations. While most of the new compounds were significantly more active than the positive control, 9, 10, 12, and 15 containing Ser and Leu at positions 10 and 11, respectively, were the most cytotoxic against MDA-MB-231, SNU449, SKOV3, DU145, and HCT116 cancer cell lines, and the 19-residue peptaibols were generally more potent than lipopeptaibols.