24-Methylenecyclopropane steroidal inhibitors: A Trojan horse in ergosterol biosynthesis that prevents growth of Trypanosoma brucei

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• 作者：Matthew B. Miller^a ; ¹ ; Presheet Patkar^a ; ¹ ; Ujjal K. Singha^b ; Minu Chaudhuri^b ; W. David Nes^a ; ^{wdavid.nes@ttu.edu}
• 关键词：HAT ; Human African trypanosomiasis ; SAM ; S-adenosyl-l-methionine ; BSF ; blood stream form ; PCF ; procyclic form ; DHL ; 26-dehydrolanosterol ; DHZ ; 26-dehydrozymosterol ; HEK ; human epithelial cells ; TbSMT ; Trypanosoma brucei sterol methyltransferase ; ED ; effective doses ; GC&ndash ; MS ; gas chromatography&ndash ; mass spectroscopy ; RRTc ; relative retention time with cholesterol used as standard
• 刊名：Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：1862
• 期：3
• 页码：305-313
• 全文大小：1195 K
• 卷排序：1862

文摘

A new class of steroidal inhibitors-mechanism-based suicide substrates- to treat sleeping sickness was studied. 26,27-Dehydrolanosterol inhibits ergosterol biosynthesis and growth of Trypanosoma brucei. 26,27-Dehydrolanosterol is a pro-drug converted in vivo to a suicide substrate of Tb-sterol methyltransferase. Kinetic and chemical mechanism of enzymic inactivation by suicide substrate is reported.