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

• Published in: ACS medicinal chemistry letters Vol. 8; no. 2; pp. 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: Journal Article
• Language: English
• Published: United States American Chemical Society 09-02-2017
• Subjects: Letter; Candida albicans; phthalazinone; isoquinolone; fluconazole; antifungal agents; synergy
• ISSN: 1948-5875; 1948-5875
• DOI: 10.1021/acsmedchemlett.6b00355

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.