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

ABSTRACT: 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.

SUBMITTER: Mood AD

PROVIDER: S-EPMC5304299 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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

Mood Aaron D AD Premachandra Ilandari Dewage Udara Anulal ID Hiew Stanley S Wang Fuqiang F Scott Kevin A KA Oldenhuis Nathan J NJ Liu Haoping H Van Vranken David L DL

ACS medicinal chemistry letters 20170111 2

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 ...[more]

PMID: 28197306

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