Estudos quantitativos de correlação estrutura-atividade em 4D de potenciais inibidores da enzima Rho quinase

Abstract

A series of pyridylthiazole derivatives developed by Lawrence, Piredduand Sebti (2013) as Rho-associated protein kinase inhibitors were subjected to four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis. The models were generated applying genetic algorithm (GA) optimization combined with partial least squares (PLS) regression. The best model presented validation values of r2 = 0.773; q2cv = 0.672; r2pred = 0.503; rm2test = 0.520; r2Y-rand = 0.19; Rp2 = 0.590. Furthermore, analysing the descriptors it was possible to propose new compounds that predicted higher inhibitory concentration values than the most active compound of the series. These compounds were submitted to docking and drug-likeness study and are promising candidates to Rock1 inhibitors.