Trichocyalides A and B, new inhibitors of alkaline phosphatase activity in bone morphogenetic protein-stimulated myoblasts, produced by Trichoderma sp FKI-5513

Two new butenolides, designated trichocyalides A and B, were isolated along with the known compound harzianolide, from the culture broth of Trichoderma sp. FKI-5513 by solvent extraction, ODS column chromatography and HPLC. Their structures were elucidated by several spectral analyses, showing that they have the common skeleton of butenofuranone. Trichocyalides A and B inhibited alkaline phosphatase (ALP) activity, a typical marker enzyme of osteoblastic differentiation (IC50: 83.0 and 187 mu M, respectively), in bone morphogenetic protein (BMP)-stimulated C2C12 myoblasts mutant cells, which stably express BMP receptor activity, whereas harzianolide showed no inhibitory activity against ALP even at 500 mu M. The Journal of Antibiotics (2012) 65, 565-569; doi: 10.1038/ja.2012.70; published online 5 September 2012