Synthesis and testing of sterol biosynthesis inhibitors with Candida albicans

dc.creatorLiu, Jialin
dc.date.available2011-02-19T01:00:08Z
dc.date.issued2002-12
dc.description.abstractA series of lanosterol analogs which contain a heteroatom substituted for C-24 or C-25 or otherwise modified in the double bond character in the sterol side chain at C-24 (25) have been prepared and assayed with Candida albicans as antifungal agents. 25- Azalanosterol and 24(R, S), 25- piminolanosterol were shown to be potent inhibitors of C. albicans growth, whereas 24-bromolanosterol, 24(28)-methylene lanosterol, 26,27- dehydrolanosterol, 4,4,14a-trimethylcholesta-8,24,26-trien-3P-ol, and 4,4,14atrimethylcholesta- 8, 24-dien-26-yne-3P-ol had no effect on growth. In the case of the ammonium-containing 25-azalanosterol and 24(i?, S), 25-epiminolanosterol, the IC50 was determined to be ca. 2.5 i^M. Eleven sterols were isolated from growth-arrested cells cultured aerobically. The identities of these compounds were established by a combination of gas chromatography; mass spectroscopy; proton nuclear magnetic resonance spectroscopy and ultra-violet spectroscopy. Ergosterol was found to be the major sterol in control cultures (63%). The sterol composition of the treated cells was found to accumulate 24-desalkyl sterol with a corresponding decrease in ergosterol. The total sterol of treated cells was increased by a factor of two compared to the wild-type control cultures. The results are interpreted to imply that the shift in the type and amount of sterol produced by treated cultures disturbs carbon flux and ergosterol homeostasis generating cell death.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/2346/22462en_US
dc.language.isoeng
dc.publisherTexas Tech Universityen_US
dc.rights.availabilityUnrestricted.
dc.subjectCandida albicansen_US
dc.subjectErgosterol -- Synthesis -- Inhibitorsen_US
dc.titleSynthesis and testing of sterol biosynthesis inhibitors with Candida albicans
dc.typeThesis
thesis.degree.departmentChemistry
thesis.degree.grantorTexas Tech University
thesis.degree.levelMasters
thesis.degree.nameM.S.

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