Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10595893 | Bioorganic & Medicinal Chemistry Letters | 2013 | 5 Pages |
Abstract
Ilicicolin H is a broad spectrum antifungal agent showing sub micro g/mL MICs against Candida spp., Aspergillus fumigatus and Cryptococcus spp. It is a potent inhibitor (C50 2-3Â ng/mL) of the mitochondrial cytochrome bc1 reductase with over 1000-fold selectivity against rat liver cytochrome bc1 reductase. Structure-activity relationship of semisynthetic derivatives by chemical modification of ilicicolin H and its 19-hydroxy derivative produced by biotransformation have been described. Basic 4â²-esters and moderately polar N- and O-alkyl derivatives retained antifungal and the cytochrome bc1 reductase activities. 4â²,19-Diacetate and 19-cyclopropyl acetate retained antifungal and enzyme activity and selectivity with over 20-fold improvement of plasma protein binding.
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Authors
Sheo B. Singh, Weiguo Liu, Xiaohua Li, Tom Chen, Ali Shafiee, Sarah Dreikorn, Viktor Hornak, Maria Meinz, Janet C. Onishi,