Amphotericin B Tamed by Salicylic Acid

Although Amphotericin B (AmB) is considered as the "gold standard" treatment for deep fungal infections, owing to its excellent antifungal its clinical use. We designed and synthesized AmB derivatives by attaching salicylic acid (SA) to the carboxyl group and confirmed their structures using 1H and measured its ultraviolet-visible (UV-vis) absorption spectrum. The AmBSA conjugates exhibited good antifungal effects against Candida albicans, Candida glabrata, and Cryptococcus neoformans compared with AmB, and the renal cytotoxicity toward HEK 293T cells in vitro was significantly reduced, with almost no nephrotoxicity in the therapeutic window of the drug. At the same time, the hemolytic toxicity was significantly reduced. Therefore, modification of AmB by introducing SA is an effective strategy to maintain the broad antifungal activity of AmB and reduce its cytotoxicity. These AmB derivatives could be applied in clinical therapy in the future.