Дата публикации: 2015

Abstract—Using the GUSAR program, structure−activity relationships on inhibition of cyclooxygenase2 (COX2) catalytic activity were quantitatively analyzed for twentysix derivatives of 4,5,6,7tetrahydro2Hisoindole, 2,3dihydro1H pyrrolyzine, and benzothiophene in the concentration range of 0.6700 nmol/liter IC50 values. Six statistically significant consensus QSAR models for prediction of IC50 values were designed based on MNA and QNAdescriptors and their com binations. These models demonstrated high accuracy in the prediction of IC50 values for structures of both training and test sets. Structural fragments of the COX2 inhibitors capable of strengthening or weakening the desired property were deter mined using the same program. This information can be taken into consideration on molecular design of new COX2 inhibitors. It was shown that in most cases, the influence of structural fragments on the inhibitory activity of the studied com pounds revealed with the GUSAR program coincided with the results of expert evaluation of their effects based on known experimental data, and this can be used for optimization of structures to change the value of their biological activity

Тип: Article

DOI: 10.1134/S0006297915010095