Repurposing benzimidazoles to fight Cryptococcus |
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| Institution: | 1. Instituto Carlos Chagas (ICC), Fundação Oswaldo Cruz (Fiocruz), Curitiba, Brazil;2. Instituto de Microbiologia Paulo de Góes (IMPG), Universidade Federal do Rio de Janeiro, Cidade Universitária, Rio de Janeiro, Brazil;1. Department of Mycology and Algology, Lomonosov Moscow State University, Moscow, 119991, Russia;2. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 117971, Russia;1. Neuroscience Division, Interdisciplinary Laboratory of Medical Investigation, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil;2. Epilepsy Treatment Advanced Centre (NATE), Felício Rocho Hospital, Belo Horizonte, MG, Brazil;3. Medicine School, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, MG, Brazil;4. Laboratório de Imunologia do Envelhecimento, Instituto de Pesquisas Biomédicas, PUCRS, Porto Alegre, RS, Brazil;5. Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands;6. NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, Queen Square, London WC1N 3BG, Epilepsy Society, Chalfont St Peter, SL9 0RJ, UK;7. Neurology Department, UNICAMP, Campinas, SP, Brazil;1. Instituto de Pesquisa e Desenvolvimento – IP&D, Universidade do Vale do Paraíba – UNIVAP, Av. Shishima Hifumi, São José dos Campos, SP 2911, Brazil;2. Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brazil;3. Natural and Humanities Sciences Center, Experimental Morphophysiology Laboratory Federal University of ABC (UFABC), Rua Arcturus, no 03, Bloco Delta, São Bernardo do Campo, SP 09606-070, Brazil |
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| 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. |
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| Keywords: | Antifungal Benzimidazoles Cryptococcosis Drug repurposing |
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