Discovery of small molecule inhibitors for the snake venom metalloprotease BaP1 using in silico and in vitro tests

 

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Autores: Villalta Romero, Fabián, Borro, Luiz, Mandic, Boris, Escalante Muñoz, Teresa, Rucavado Romero, Alexandra, Gutiérrez, José María, Neshich, Goran, Tasic, Ljubica
Formato: artículo original
Data de Publicação:2017
Descrição:Snakebites represent an important public health problem, with a great number of victims with perma nent sequelae or fatal outcomes, particularly in rural, agriculturally active areas. The snake venom met alloproteases (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 neutraliz ing 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 aforemen tioned approaches provided strong evidences on the structural requirements for the efficient BaP1 inhi bition 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.
País:Kérwá
Recursos:Universidad de Costa Rica
Repositorio:Kérwá
Idioma:Inglés
OAI Identifier:oai:kerwa.ucr.ac.cr:10669/103839
Acesso em linha:https://hdl.handle.net/10669/103839
https://doi.org/10.1016/j.bmcl.2017.03.007
Palavra-chave:snake venom metalloproteases
inhibitors
high through virtual screening
in vitro interaction studies