Soumitra Guin, Kathryn M. Alden, Damian J. Krysan* and Marvin J. Meyers*,
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引用次数: 0
Abstract
Cryptococcal neoformans and Candida albicans are among the most prevalent causes of life-threatening fungal infections globally. The high mortality associated with these infections despite current antifungal therapy highlights the need for new drugs. In our previous work, we demonstrated that an analogue of the clinically used antimalarial mefloquine, (8-chloro-2-(4-chlorophenyl)quinolin-4-yl)(piperidin-2-yl)methanol (4377), has both antifungal activity and the ability to penetrate the central nervous system. Herein we describe the synthesis and antifungal assay of all four stereoisomers of 4377. All four stereoisomers retain potent antifungal activity with the erythro enantiomers having MIC values of 1 and 4 μg/mL against C. neoformans and C. albicans, respectively, and threo enantiomers, MIC values of 2 and 8 μg/mL, respectively. These results indicate that the stereochemistry of the piperidine methanol group is not critical for the antifungal properties of 4377 and gives guidance to future medicinal chemistry optimization efforts.
期刊介绍:
ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to:
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Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry
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Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response
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