Drug repositioning of benzimidazole anthelmintics in the treatment of cryptococcosis: a review

• Published in: Medicinal chemistry research Vol. 31; no. 1; pp. 26 - 39
• Main Authors: Oliveira, Emanuel A. M., Ferreira, Gabriella F., Lang, Karen L.
• Format: Journal Article
• Language: English
• Published: New York Springer US 2022; Springer Nature B.V
• Subjects: Albendazole; Anthelmintic agents; Antifungal activity; Benzimidazoles; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Cryptococcosis; Drug development; Drugs; Fungal infections; Fungi; Fungicides; Health services; Inorganic Chemistry; Lethality; Mebendazole; Medicinal Chemistry; Meningitis; Morbidity; Mycosis; Pharmacology/Toxicology; R&D; Research & development; Review Article; Scaffolds; Toxicity; Drug repurposing; Drug repositioning; Benzimidazole anthelmintics; Anticryptococcal agents; Cryptococcosis
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-021-02824-4

Cryptococcosis is a systemic mycosis caused by pathogenic yeasts of the Cryptococcus genus and the second biggest cause of morbidity and mortality in individuals with AIDS. Cryptococcal meningitis is the most severe form of the disease, with high lethality rates. Currently, only three antifungals drugs are approved for the treatment of cryptococcosis, which present high toxicity, low efficacy, high costs, and limited availability in several countries. The need for new antifungals for the treatment of systemic mycosis is clear; however, drug research and development is costly and time-consuming. Drug repositioning is a strategy that has been promising for the development of new therapeutic alternatives for diseases that suffer from scarce therapeutic resources, such as cryptococcosis, as it presents a considerable reduction in costs, risks, and research time. Some drug candidates for repositioning share structural similarities with each other that may reflect a scaffold in the discovery of new anticryptococcal agents. The anthelmintics drugs albendazole, flubendazole, mebendazole, and fenbendazole showed potent in vitro antifungal activity apparently related to the benzimidazole scaffold present in these drugs. Thus, this non-systematic review discusses recent data about benzimidazole anthelmintic drugs as promising candidates for repositioning in the treatment of cryptococcosis.