Repurposing benzimidazoles to fight Cryptococcus

Abstract

The human diseases caused by the fungal pathogens Cryptococcus neoformans and Cryptococcus gattii are associated with high rates of mortality and toxic or cost-prohibitive therapeutic protocols. The need for affordable antifungals to combat cryptococcal disease is unquestionable. Benzimidazoles are potentially attractive antifungal compounds that were introduced in clinical practice nearly 60 years ago to treat helminthic infections. In addition to being safe, their cost of treatment is extraordinarily low. Several studies suggested benzimidazoles as promising anticryptococcal agents combining low-cost and high antifungal efficacy. So far, anti-cryptococcal activities were demonstrated for 16 different benzimidazoles. In particular, albendazole, mebendazole, flubendazole, and fenbendazole have potent in vitro antifungal activity against C. neoformans and C. gattii. Mice lethally infected with C. neoformans and treated with fenbendazole had 100 % survival when the drug was administered intranasally. In this review, we discuss the potential of benzimidazoles as potential anti-cryptococcal agents, including a general literature overview, most recent findings, mechanism of antifungal action, costs, toxicity, and antifungal potential in vivo.