Potent Antifungal Synergy of Phthalazinone and Isoquinolones with Azoles Against <i>Candida albicans</i>

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 <i>Candida albicans</i>. Several even more potent analogues of these compounds were identified, some with EC₅₀ as low as 1 nM, against <i>C. albicans</i>. 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 <b>15</b> and phthalazinone <b>24</b> were shown to be active against several resistant clinical isolates of <i>C. albicans</i>.