QSAR analysis of antitumor active amides and quinolones from thiophene series

QSAR models for predicting antitumor activity of heterocyclic amides and quinolones from benzo[b]thiophene-, thieno[3,2-b]thiophene- and thieno[2,3-b], thiophene series against MiaPaCa-2 and MCF-7 cells were built. Complete dataset consisted of 59 compounds and several QSAR models with different predictive ability were derived. Beside standard approaches for building QSAR models, the approach based on a small dataset of 10 compounds selected regarding the results of principal component analysis was tested. The latter approach was shown as successful and can be useful for planning future experiments in order to speed up and simplify the search for new drug candidates. Based on the derived QSAR models, the most important properties for compound's antitumor activity against MiaPaCa-2 and MCF-7 cells were identified. Volume, sum of the hydrophobic surfaces and presence of the group that can be easily ionized in the pH range from 4 to 9, were found to be highly important for successful antitumor activity of the examined heterocyclic amides and quinolones. New compounds, with potentially higher biological activity against MiaPaCa-2 and MCF-7 cells, were proposed. Their activities were predicted using the derived QSAR models and the proposed compounds were shown as promising antitumor candidates. (C) 2010 Elsevier B.V. All rights reserved.