synthetic arylquinuclidine derivatives exhibit antifungal activity against candida albicans, candida tropicalis and candida parapsilopsis合成arylquinuclidine衍生品具有活性抗真菌对白色念珠菌、念珠菌tropicalis和念珠菌parapsilopsis.pdfVIP

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synthetic arylquinuclidine derivatives exhibit antifungal activity against candida albicans, candida tropicalis and candida parapsilopsis合成arylquinuclidine衍生品具有活性抗真菌对白色念珠菌、念珠菌tropicalis和念珠菌parapsilopsis.pdf

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synthetic arylquinuclidine derivatives exhibit antifungal activity against candida albicans, candida tropicalis and candida parapsilopsis合成arylquinuclidine衍生品具有活性抗真菌对白色念珠菌、念珠菌tropicalis和念珠菌parapsilopsis

Ishida et al. Annals of Clinical Microbiology and Antimicrobials 2011, 10:3 /content/10/1/3 RESEARCH Open Access Synthetic arylquinuclidine derivatives exhibit antifungal activity against Candida albicans, Candida tropicalis and Candida parapsilopsis 1 2 3 4 3 Kelly Ishida , Juliany Cola Fernandes Rodrigues , Simon Cammerer , Julio A Urbina , Ian Gilbert , Wanderley de Souza2,5, Sonia Rozental1* Abstract Background: Sterol biosynthesis is an essential pathway for fungal survival, and is the biochemical target of many antifungal agents. The antifungal drugs most widely used to treated fungal infections are compounds that inhibit cytochrome P450-dependent C14a-demethylase (CYP51), but other enzymes of this pathway, such as squalene synthase (SQS) which catalyses the first committed step in sterol biosynthesis, could be viable targets. The aim of this study was to evaluate the antifungal activity of SQS inhibitors on Candida albicans, Candida tropicalis and Candida parapsilopsis strains. Methods: Ten arylquinuclidines that act as SQS inhibitors were tested as antiproliferative agents against three ATCC strains and 54 clinical isolates of Candida albicans, Candida tropicalis and Candida parapsilopsis. Also, the morphological alterations induced in the yeasts by the experimental compounds were evaluated by fluorescence and transmission electron microscopy. Results: The most potent arylquinuclidine derivative (3-[1’-{4’-(benzyloxy)-phenyl}]-quinuclidine-2-ene) (WSP1267) had a MIC50 of 2 μg/ml for all species tested and MIC90 varying from 4 μg/ml to 8 μg/ml. Ultrathin sections of C. albicans treated with 1 μg/ml of WSP1267 showed several ultrastructural alterations, including (a) loss of cell wall