steroidal triterpenes design of substrate-based inhibitors of ergosterol and sitosterol synthesis甾族的三萜substrate-based麦角固醇和谷甾醇合成的抑制剂的设计.pdf

Molecules 2009, 14, 4690-4706; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review Steroidal Triterpenes: Design of Substrate-Based Inhibitors of Ergosterol and Sitosterol Synthesis Jialin Liu and William David Nes * Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas, 79409, USA; E-Mail: jialin.liu@ (J.L.) * Author to whom correspondence should be addressed; E-Mail: wdavid.nes@. Received: 22 September 2009; in revised form: 5 November 2009 / Accepted: 10 November 2009 / Published: 18 November 2009 Abstract: This article reviews the design and study, in our own laboratory and others, of new steroidal triterpenes with a modified lanosterol or cycloartenol frame. These compounds, along with a number of known analogs with the cholestane skeleton, have been evaluated as reversible or irreversible inhibitors of sterol C24-methyltransferase (SMT) from plants, fungi and protozoa. The SMT catalyzes the C24-methylation reaction involved with the introduction of the C24-methyl group of ergosterol and the C24-ethyl group of sitosterol, cholesterol surrogates that function as essential membrane inserts in many photosynthetic and non-photosynthetic eukaryotic organisms. Sterol side chains constructed with a nitrogen, sulfur, bromine or fluorine atom, altered to possess a methylene cy