Novel Water-Soluble Amphotericin B-PEG Conjugates with Low Toxicity and Potent in Vivo Efficacy

Assaf Halperin, Yana Shadkchan, Evgeni Pisarevsky, Alex M. Szpilman*, Hani Sandovsky, Nir Osherov, Itai Benhar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Systemic fungal infections are an increasingly prevalent health problem, especially among immunocompromised patients. Antifungal drug development lags far behind in comparison to other types of antimicrobial drugs. Current commercially available antifungals are limited by their insufficient potency, side effects, drug-drug interactions, developing drug-resistance, and narrow formulation options. Here, we report the preparation and evaluation of two novel PEG amide conjugates of amphotericin B (AMB (1)): AB1 (4) and AM2 (5). These compounds are nonlabile, they are prepared in only two and three synthetic steps, respectively, and they show antifungal activity against a wide range of clinical fungal isolates. Their toxicity is significantly lower, and their water solubility is up to 5000-fold higher than that of AMB (1). In vivo efficacy studies in a mouse model of systemic candidiasis showed that AM2 (5) successfully cured all the mice at concentrations above 3.5 mg/kg body weight. In conclusion, these properties make AB1 (4) and AM2 (5) promising candidates for clinical use.

Original languageEnglish
Pages (from-to)1197-1206
Number of pages10
JournalJournal of Medicinal Chemistry
Issue number3
StatePublished - 11 Feb 2016


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