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Molecules 2009, 14(11), 4690-4706; doi:10.3390/molecules14114690
Review

Steroidal Triterpenes: Design of Substrate-Based Inhibitors of Ergosterol and Sitosterol Synthesis

 and *
Received: 22 September 2009; in revised form: 5 November 2009 / Accepted: 10 November 2009 / Published: 18 November 2009
(This article belongs to the Special Issue Triterpenes and Triterpenoids)
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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 cyclopropane group, or elongated to include terminal double or triple bonds are shown to exhibit different in vitro activities toward the SMT which are mirrored in the inhibition potencies detected in the growth response of treated cultured human and plant cells or microbes. Several of the substrate-based analogs surveyed here appear to be taxaspecific compounds acting as mechanism-based inactivators of the SMT, a crucial enzyme not synthesized by animals. Possible mechanisms for the inactivation process and generation of novel products catalyzed by the variant SMTs are discussed.
Keywords: sterol C24-methyltransferase (24-SMT); transition state analogs; mechanismbased inactivator; ergosterol biosynthesis inhibitors; ergosterol; sitosterol; triterpenes sterol C24-methyltransferase (24-SMT); transition state analogs; mechanismbased inactivator; ergosterol biosynthesis inhibitors; ergosterol; sitosterol; triterpenes
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Liu, J.; Nes, W.D. Steroidal Triterpenes: Design of Substrate-Based Inhibitors of Ergosterol and Sitosterol Synthesis. Molecules 2009, 14, 4690-4706.

AMA Style

Liu J, Nes WD. Steroidal Triterpenes: Design of Substrate-Based Inhibitors of Ergosterol and Sitosterol Synthesis. Molecules. 2009; 14(11):4690-4706.

Chicago/Turabian Style

Liu, Jialin; Nes, William David. 2009. "Steroidal Triterpenes: Design of Substrate-Based Inhibitors of Ergosterol and Sitosterol Synthesis." Molecules 14, no. 11: 4690-4706.


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