真菌莫氏菌属SANK 10294产生的角鲨烯合酶强效抑制剂扎拉戈昔酸D3对蛋白质异戊二烯化的抑制活性及抗真菌活性

Inhibitory activity to protein prenylation and antifungal activity of zaragozic acid D3, a potent inhibitor of squalene synthase produced by the fungus, Mollisia sp. SANK 10294.

作者信息

Tanimoto T, Ohya S, Tsujita Y

机构信息

Pharmacology Laboratory, Sankyo Co., Ltd., Tokyo, Japan.

出版信息

J Antibiot (Tokyo). 1998 Apr;51(4):428-31. doi: 10.7164/antibiotics.51.428.

DOI:10.7164/antibiotics.51.428

PMID:9630865

Abstract

Recently we found novel zaragozic acids (ZAs), F-10863A (zaragozic acid D3, ZAD3), B, C and D in the culture broth of the fungus Mollisia sp. SANK 10294 as potent inhibitors of squalene synthase. There are several other enzymes that use farnesylpyrophosphate as their substrate. Among them we chose farnesyl-protein transferase and examined whether ZAD3 and F-10863B inhibit this enzyme's activity. ZAD3 and F-10863B inhibited farnesyl-protein transferase with IC50 values of 0.60 and 3.7 microM, respectively. They also inhibited geranylgeranyl-protein transferase at similar concentrations. In addition, they exhibited potent antifungal activity.

摘要

最近，我们在真菌莫氏菌属SANK 10294的培养液中发现了新型扎拉戈酸（ZAs），即F-10863A（扎拉戈酸D3，ZAD3）、B、C和D，它们是角鲨烯合酶的强效抑制剂。还有其他几种以法尼基焦磷酸为底物的酶。在这些酶中，我们选择了法尼基蛋白转移酶，并检测ZAD3和F-10863B是否能抑制该酶的活性。ZAD3和F-10863B抑制法尼基蛋白转移酶的IC50值分别为0.60和3.7微摩尔。它们在相似浓度下也能抑制香叶基香叶基蛋白转移酶。此外，它们还表现出强效的抗真菌活性。