| Autor: |
Pereira ALE; a Laboratório de Pesquisas Forenses e Genômica, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto , University of São Paulo , Ribeirão Preto , Brazil., Dos Santos GB; b Computational Laboratory of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto , University of São Paulo , Ribeirão Preto , São Paulo , Brazil., Franco MSF; b Computational Laboratory of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto , University of São Paulo , Ribeirão Preto , São Paulo , Brazil., Federico LB; b Computational Laboratory of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto , University of São Paulo , Ribeirão Preto , São Paulo , Brazil., da Silva CHTP; b Computational Laboratory of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto , University of São Paulo , Ribeirão Preto , São Paulo , Brazil., Santos CBR; b Computational Laboratory of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto , University of São Paulo , Ribeirão Preto , São Paulo , Brazil.; c Laboratory of Modeling and Computational Chemistry, Department of Biological Sciences , Federal University of Amapá , 68902-280 Macapá , AP , Brazil. |
| Abstrakt: |
Human dipeptidyl peptidase IV (hDDP-IV) has a considerable importance in inactivation of glucagon-like peptide-1, which is related to type 2 diabetes. One approach for the treatment is the development of small hDDP-IV inhibitors. In order to design better inhibitors, we analyzed 5-(aminomethyl)-6-(2,4-dichlrophenyl)-2-(3,5-dimethoxyphenyl)pyrimidin-4-amine and a set of 24 molecules found in the BindingDB web database for model designing. The analysis of their molecular properties allowed the design of a multiple linear regression model for activity prediction. Their docking analysis allowed visualization of the interactions between the pharmacophore regions and hDDP-IV. After both analyses were performed, we proposed a set of nine molecules in order to predict their activity. Four of them displayed promising activity, and thus, had their docking performed, as well as, the pharmacokinetic and toxicological study. Two compounds from the proposed set showed suitable pharmacokinetic and toxicological characteristics, and therefore, they were considered promising for future synthesis and in vitro studies. |
