Identification and validation of P. berghei glutathione s‐transferase small molecule inhibitors by virtual library screening (LB274)

Autor:	José G. Ortiz, Adelfa E. Serrano, Jürgen Bosch, Emilee E. Colón-Lorenzo, Daisy D. Colón-López
Rok vydání:	2014
Předmět:	Drug biology media_common.quotation_subject In silico Computational biology Drug resistance Biochemistry Molecular biology Small molecule Reverse genetics Glutathione S-transferase Drug development Genetics biology.protein Molecular Biology Gene Biotechnology media_common
Zdroj:	The FASEB Journal. 28
ISSN:	1530-6860 0892-6638
Popis:	Antimalarial drug development is of outmost importance to achieve malaria eradication, especially by targeting the blood stages critical to parasite development. Identification and validation of potential drug targets is required for the development of novel antimalarials. Glutathione S-transferase (GST) is a detoxification enzyme that has been associated with drug resistance and proposed as a potential drug target in Plasmodium. This study aims to elucidate the biological role of pbGST using a combination of reverse genetics and bioinformatics approaches. Multiple attempts to disrupt the pbgst gene were unsuccessful indicating that GST is essential for P. berghei erythrocytic stages; validating pbGST as a drug target. A pbGST structural model was generated by comparative modeling and used to perform a virtual library screening of the ChEMBL-Neglected Tropical Disease library and the ChemBridge Express library using the OpenEye software suite. In silico screening identified several hits with potential as ...
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::50e9561c9be168a545c6f2bfa1e1a4e4 https://doi.org/10.1096/fasebj.28.1_supplement.lb274 Zobrazit plný text záznamu Plný text