Potent Antifungal Synergy of Phthalazinone and Isoquinolones with Azoles Against Candida albicans

Four phthalazinones (CIDs 22334057, 22333974, 22334032, 22334012) and one isoquinolone (CID 5224943) were previously shown to be potent enhancers of antifungal activity of fluconazole against Candida albicans. Several even more potent analogues of these compounds were identified, some with EC50 as l...

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Bibliographic Details
Published in:ACS medicinal chemistry letters 2017-02, Vol.8 (2), p.168-173
Main Authors: Mood, Aaron D., Premachandra, Ilandari Dewage Udara Anulal, Hiew, Stanley, Wang, Fuqiang, Scott, Kevin A., Oldenhuis, Nathan J., Liu, Haoping, Van Vranken, David L.
Format: Article
Language:English
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Letter
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Summary:Four phthalazinones (CIDs 22334057, 22333974, 22334032, 22334012) and one isoquinolone (CID 5224943) were previously shown to be potent enhancers of antifungal activity of fluconazole against Candida albicans. Several even more potent analogues of these compounds were identified, some with EC50 as low as 1 nM, against C. albicans. The compounds exhibited pharmacological synergy (FIC < 0.5) with fluconazole. The compounds were also shown to enhance the antifungal activity of isavuconazole, a recently FDA approved azole antifungal. Isoquinolone 15 and phthalazinone 24 were shown to be active against several resistant clinical isolates of C. albicans.
ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.6b00355