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

Aaron D Mood; Ilandari Dewage Udara Anulal Premachandra; Stanley Hiew; Fuqiang Wang; Kevin A Scott; Nathan J Oldenhuis; Haoping Liu; David L Van Vranken

doi:10.1021/acsmedchemlett.6b00355

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

ACS Med Chem Lett. 2017 Jan 11;8(2):168-173. doi: 10.1021/acsmedchemlett.6b00355. eCollection 2017 Feb 9.

Authors

Aaron D Mood¹, Ilandari Dewage Udara Anulal Premachandra¹, Stanley Hiew¹, Fuqiang Wang², Kevin A Scott¹, Nathan J Oldenhuis¹, Haoping Liu², David L Van Vranken¹

Affiliations

¹ Department of Chemistry, University of California , 1102 Natural Sciences 2, Irvine, California 92697-2025, United States.
² Department of Biological Chemistry, University of California , Irvine, California 92697-1700, United States.

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.

Keywords: Candida albicans; antifungal agents; fluconazole; isoquinolone; phthalazinone; synergy.

Abstract

Grants and funding