Busca de inibidores multialvo das enzimas CYP51 e DECR de trypanosoma cruzi para o tratamento da doença de Chagas

• Autor(a) principal: Pereira, Ronniery Ilario
• Data de Publicação: 2019
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações do LNCC
• Texto Completo: https://tede.lncc.br/handle/tede/322
• topic: Reposicionamento de fármacos; Chagas, Doença de; Família 51 do Citocromo P450; Ancoragem molecular; Docking Molecular; CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA

Computational techniques for modeling molecules have been shown to be indispensable for the development of new drugs by reducing the cost, time and side effects by making the molecular target of the molecule under study more specific. This methodology is being used in the strategy of repositioning drugs for neglected diseases such as Chagas disease, whose treatment still has many side effects. In this work we aim to search for multi-target inhibitors of the enzymes CYP51 and DECR, considered potential therapeutic targets for the treatment of Chagas disease. Through the molecular docking technique using the Glide software, the mode and affinity of several compounds at the active site of the targets were evaluated. Library of ligands were used, containing molecules approved by the FDA and other compounds synthesized by collaborators such as LASSBio-UFRJ. The compounds cangrelor and bedaquiline showed good values of interaction affinity with the enzymes studied in this work. For the LASSBio database, the compounds LASSBio457, LASSBio460 and LASSBio558 proved to be promising multi-target compounds.