期刊论文详细信息
Journal of the Brazilian Chemical Society
Structure-based drug design studies on a series of aldolase inhibitors
Leonardo G. Ferreira1  Ricardo N. Dos Santos1  Adriano D. Andricopulo1 
[1],Universidade de São Paulo Instituto de Física de São Carlos Laboratório de Química Medicinal e ComputacionalSão Carlos SP ,Brazil
关键词: African trypanosomiasis;    drug;    design;    inhibitors;    QSAR;    molecular modeling;   
DOI  :  10.5935/0103-5053.20130026
来源: SciELO
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【 摘 要 】
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, and 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.
【 授权许可】

CC BY   
 All the contents of this journal, except where otherwise noted, is licensed under a Creative Commons Attribution License

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