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QSAR analysis and proposal of new heterocyclic compounds with potential antitumor activity

Quantitative Structure–Activity Relationship (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 were built. Dataset consisted of 56 compounds with measured antitumor activity. For each compound VolSurf descriptors were derived and correlated with the biological activity using Partial Least Square analysis. 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 (PCA), was tested. The latter approach was shown as successful and it seems useful for planning experiments in order to speed up and simplify the search for new drug candidates. Results of PCA and QSAR analysis enabled identification of molecular properties with the highest impact on antitumor activity. Volume, sum of the hydrophobic surface areas 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 investigated compounds.[1] Using this knowledge, new compounds were proposed for synthesis and biological testing. Their activities were predicted using the derived QSAR models and the proposed compounds were shown as promising antitumor candidates.

QSAR; VolSurf; Antitumor activity; Quinolones

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