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Discovery of small molecule inhibitors for the snake venom metalloprotease BaP1 using in silico and in vitro tests.
Villalta-Romero, Fabian; Borro, Luiz; Mandic, Boris; Escalante, Teresa; Rucavado, Alexandra; Gutiérrez, Jose María; Neshich, Goran; Tasic, Ljubica.
Afiliação
  • Villalta-Romero F; Chemical Biology Laboratory, Organic Chemistry Department, Institute of Chemistry, UNICAMP, Campinas, SP, Brazil.
  • Borro L; Institute of Biology, UNICAMP, Campinas, SP, Brazil.
  • Mandic B; Chemical Biology Laboratory, Organic Chemistry Department, Institute of Chemistry, UNICAMP, Campinas, SP, Brazil; Faculty of Chemistry, University of Belgrade, Belgrade, Serbia.
  • Escalante T; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
  • Rucavado A; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
  • Gutiérrez JM; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
  • Neshich G; Brazilian Agricultural Research Corporation (EMBRAPA), National Center for Agricultural Informatics, Computational Biology Research Group, Campinas, SP, Brazil.
  • Tasic L; Chemical Biology Laboratory, Organic Chemistry Department, Institute of Chemistry, UNICAMP, Campinas, SP, Brazil. Electronic address: ljubica@iqm.unicamp.br.
Bioorg Med Chem Lett ; 27(9): 2018-2022, 2017 05 01.
Article em En | MEDLINE | ID: mdl-28347665
Snakebites represent an important public health problem, with a great number of victims with permanent sequelae or fatal outcomes, particularly in rural, agriculturally active areas. The snake venom metalloproteases (SVMPs) are the principal proteins responsible for some clinically-relevant effects, such as local and systemic hemorrhage, dermonecrosis, and myonecrosis. Because of the difficulties in neutralizing them rapidly and locally by antivenoms, the search and design of small molecules as inhibitors of SVMPs are proposed. The Bothrops asper metalloprotease P1 (BaP1) is hereby used as a target protein and by High Throughput Virtual Screening (HTVS) approach, the free access virtual libraries: ZINC, PubChem and ChEMBL, were searched for potent small molecule inhibitors. Results from the aforementioned approaches provided strong evidences on the structural requirements for the efficient BaP1 inhibition such as the presence of the pyrimidine-2,4,6-trione moiety. The two proposed compounds have also shown excellent results in performed in vitro interaction studies against BaP1.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirimidinonas / Venenos de Serpentes / Metaloendopeptidases / Bothrops / Antídotos Limite: Animals Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirimidinonas / Venenos de Serpentes / Metaloendopeptidases / Bothrops / Antídotos Limite: Animals Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido