Structure-based drug design studies on a series of aldolase inhibitors
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
---|---|
Data(s) |
28/05/2014
28/05/2014
2013
|
Resumo |
Human African trypanosomiasis, also known as sleeping sickness, is a major cause of death in Africa, and for which there are no safe and effective treatments available. The enzyme aldolase from Trypanosoma brucei is an attractive, validated target for drug development. A series of alkyl‑glycolamido and alkyl-monoglycolate derivatives was studied employing a combination of drug design approaches. Three-dimensional quantitative structure-activity relationships (3D QSAR) models were generated using the comparative molecular field analysis (CoMFA). Significant results were obtained for the best QSAR model (r2 = 0.95, non-cross-validated correlation coefficient, and q2 = 0.80, cross-validated correlation coefficient), indicating its predictive ability for untested compounds. The model was then used to predict values of the dependent variables (pKi) of an external test set,the predicted values were in good agreement with the experimental results. The integration of 3D QSAR, molecular docking and molecular dynamics simulations provided further insight into the structural basis for selective inhibition of the target enzyme. FAPESP CNPq |
Identificador |
Journal of the Brazilian Chemical Society, São Paulo : Sociedade Brasileira de Química - SBQ, v. 24, n. 2, p. 201-211, 2013 0103-5053 http://www.producao.usp.br/handle/BDPI/45103 10.5935/0103-5053.20130026 |
Idioma(s) |
eng |
Publicador |
Sociedade Brasileira de Química - SBQ São Paulo |
Relação |
Journal of the Brazilian Chemical Society |
Direitos |
openAccess Copyright Sociedade Brasileira de Química |
Palavras-Chave | #African trypanosomiasis #Drug #Design #Inhibitors #QSAR #Molecular modeling #TRYPANOSOMA #ENZIMAS #PLANEJAMENTO DE FÁRMACOS |
Tipo |
article original article publishedVersion |