Use este identificador para citar ou linkar para este item: http://repositorio.bc.ufg.br/handle/ri/15744
Tipo do documento: Artigo
Título: Alkaloids as inhibitors of malate synthase from paracoccidioides spp.: receptor-ligand interaction-based virtual screening and molecular docking studies, antifungal activity and the adhesion process
Autor: Costa, Fausto Guimaraes
Silva Neto, Benedito Rodrigues da
Gonçalves, Ricardo Lemes
Silva, Roosevelt Alves da
Oliveira, Cecília Maria Alves de
Kato, Lucília
Freitas, Carla dos Santos
Giannini, Maria José Soares Mendes
Silva, Julhiany de Fátima da
Soares, Célia Maria de Almeida
Pereira, Maristela
Abstract: Paracoccidioides is the agent of paracoccidioidomycosis. Malate synthase plays a crucial role in the pathogenicity and virulence of various fungi, such as those that are human pathogens. Thus, an inhibitor of this enzyme may be used as a powerful antifungal without side effects in patients once these enzymes are absent in humans. Here, we searched for compounds with inhibitory capacity against the malate synthase of Paracoccidioides species (PbMLS). The three-dimensional (3D) structure of PbMLS was determined using the I-TASSER server. Compounds were selected from the ZINC database. Based on the mechanism underlying the interaction of the compounds with PbMLS, it was possible to identify -carboline moiety as a standard key structure. The compounds with -carboline moiety that are available in our laboratories were investigated. A total of nine alkaloid compounds were selected. The primary mechanisms of interaction of the alkaloid compounds in the binding pocket of PbMLS were identified and compared with the mechanism of interaction of acetyl coenzyme A (acetyl-CoA). We discovered that the amphipathic nature of the compounds, concomitant with the presence of -carboline moiety, was crucial for their stability in the binding pocket of PbMLS. In addition, the importance of a critical balance of the polar and nonpolar contacts of the compounds in this region was observed. Four -carboline alkaloid compounds showed the ability to inhibit recombinant PbMLS (PbMLSr) activity, Paracoccidioides species growth, and adhesion of the fungus and PbMLSr to the extracellular matrix components. The cytotoxicity of the alkaloids was also evaluated.
País: Estados unidos
Unidade acadêmica: Instituto de Química - IQ (RG)
Citação: COSTA, Fausto Guimaraes et al. Alkaloids as inhibitors of malate synthase from paracoccidioides spp.: receptor-ligand interaction-based virtual screening and molecular docking studies, antifungal activity and the adhesion process. Antimicrobial Agents and Chemotherapy, Washington, v. 59, n. 9, p. 5581-5594, Sept. 2015.
Tipo de acesso: Acesso Aberto
Identificador do documento: 10.1128/AAC.04711-14
Identificador do documento: 10.1128/AAC.04711-14
URI: http://repositorio.bc.ufg.br/handle/ri/15744
Data de publicação: Set-2015
Aparece nas coleções:IQ - Artigos publicados em periódicos

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