Aspartic Proteolytic Inhibitors Induce Cellular and Biochemical Alterations in Fungal Cells
Although fungal infections contribute substantially to human morbidity and mortality, the impact of these diseases on human health is not widely appreciated. Diagnosis and treatment of fungal infections remain a challenge in medicine despite recent major
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stract Although fungal infections contribute substantially to human morbidity and mortality, the impact of these diseases on human health is not widely appreciated. Diagnosis and treatment of fungal infections remain a challenge in medicine despite recent major advances. The search for novel pharmacological compounds with antifungal action is a real requirement. Taking it into consideration, research groups have investigated the effects of aspartic peptidase inhibitors (PIs) on the development of human fungal pathogens such as Candida spp, mainly Candida
A.L.S. Santos (*) • L.A. Braga-Silva Laboratório de Investigação de Peptidases, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Bloco E-subsolo, Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil Programa de Pós-Graduação em Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil e-mail: [email protected]; [email protected] B.A. Silva Departamento de Ciências Básicas, Pólo Universitário de Nova Friburgo, Universidade Federal Fluminense (UFF), Nova Friburgo, Rio de Janeiro, Brazil V.F. Palmeira • R.S. Valle • É.A. Abi-chacra Laboratório de Investigação de Peptidases, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Bloco E-subsolo, Centro de Ciências da Saúde (CCS), Universidade Federal Fluminense (UFF), Nova Friburgo, Rio de Janeiro, Brazil V.S. Oliveira • R.D. Lins Laboratório de Modelagem de Biomateriais, Departamento de Química Fundamental, Universidade Federal de Pernambuco (UFPE), Pernambuco, Brazil L.F. Kneipp Laboratório de Taxonomia, Bioquímica e Bioprospecção de Fungos, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil C.L. Sodré Departamento de Biologia Celular e Molecular, Intituto de Biologia, Universidade Federal Fluminense (UFF), Niterói, Rio de Janeiro, Brazil S. Chakraborti and N.S. Dhalla (eds.), Proteases in Health and Disease, Advances in Biochemistry in Health and Disease 7, DOI 10.1007/978-1-4614-9233-7_7, © Springer Science+Business Media New York 2013
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albicans and Candida parapsilosis, Cryptococcus neoformans, Pneumocystis jiroveci and Fonsecaea pedrosoi, based on the following premises: (1) this class of hydrolytic enzymes performs multiple relevant roles in pathophysiological events associated to the fungal infections and (2) the introduction of human immunodeficiency virus (HIV) PIs in the clinical arena drastically reduced the opportunistic infections caused by fungi in this population. As expected, the blockage of one of these physiological/pathological processes should help in containing the fungal infection. Corroborating this hypothesis, both in vitro and in vivo studies have reported that classical aspartic PIs (e.g., pepstatin A) as well as HIV PIs (e.g., nelfinavir, saquinavir, ritonavir, indinavir, amprenavir, lopinavir and tipranavir) have induced several cellular and biochemical al
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