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

• Ano de defesa: 2016
• Autor(a) principal: Gajo, Giovanna Cardoso
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Lavras; Programa de Pós-Graduação em Agroquímica; UFLA; brasil; Departamento de Química
• Palavras-chave em Português: Enzimas – Análise; Inibidores enzimáticos; Ancoramento molecular; Metodologia QSAR; Patologia; Rho quinase (ROCK); Enzymes – Analysis; Enzyme inhibitors; Docking; QSAR methodology; Pathology; Enzimologia
• Link de acesso: http://repositorio.ufla.br/jspui/handle/1/11177

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.