Hosoe T, Okada H, Itabashi T, Nozawna K, Okada K, Takaki G M, Fukushima K, Miyaji M, Kawai K
Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Chem Pharm Bull (Tokyo). 2000 Oct;48(10):1422-6. doi: 10.1248/cpb.48.1422.
In the course of searching for new antifungal agents, a new pentanorlanostane derivative, cladosporide A (1), was isolated along with ergosterol, ergosterol peroxide and 23,24,25,26,27-pentanorlanost-8-ene-3beta,22-diol (2) from Cladosporium sp. as a characteristic antifungal agent against the human pathogenic filamentous fungus Aspergillus fumigatus. The structure of 1 was established as 3beta,22-dihydroxy-23,24,25,26,27-pentanorlanostane-29-al by spectroscopic and chemical investigation and X-ray crystallographic analysis. Inhibitory activity against A. fumigatus (IC80 0.5-4.0 microg/ml) was observed for cladosporide A (1), but no activity was observed against pathogenic yeasts, Candida albicans and Cryptococcus neoformans, and other pathogenic filamentous fungi, Aspergillus niger and A. flavus. The 4beta-aldehyde residue in 1 might be essential for the antifungal activity, since 23,24,25,26,27-pentanorlanost-8-ene-3beta,22-diol (2) showed no inhibition against the above four fungi.
在寻找新型抗真菌剂的过程中，从枝孢属真菌中分离出一种新的五环羊毛甾烷衍生物枝孢菌素A（1），同时还分离出了麦角甾醇、过氧化麦角甾醇和23,24,25,26,27-五降羊毛甾-8-烯-3β,22-二醇（2），枝孢菌素A是一种对人类致病丝状真菌烟曲霉具有特征性抗真菌活性的物质。通过光谱、化学研究及X射线晶体学分析确定1的结构为3β,22-二羟基-23,24,25,26,27-五降羊毛甾烷-29-醛。观察到枝孢菌素A（1）对烟曲霉具有抑制活性（IC80为0.5 - 4.0微克/毫升），但对致病性酵母白色念珠菌和新型隐球菌以及其他致病丝状真菌黑曲霉和黄曲霉没有活性。1中的4β-醛基残基可能是抗真菌活性所必需的，因为23,24,25,26,27-五降羊毛甾-8-烯-3β,22-二醇（2）对上述四种真菌均无抑制作用。
