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...

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Bibliographic Details
Published in:International journal of pharmaceutics 2010-07, Vol.394 (1), p.106-114
Main Authors: BERTOSA, B, ALEKSIC, M, KARMINISKI-ZAMOLA, G, TOMIC, S
Format: Article
Language:English
Subjects:
Amides - chemistry
Amides - pharmacology
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antitumor activity
Biological and medical sciences
Cell Line, Tumor
Drug Screening Assays, Antitumor
General pharmacology
Humans
Hydrogen-Ion Concentration
Hydrophobic and Hydrophilic Interactions
Medical sciences
Models, Molecular
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Principal Component Analysis
QSAR
Quantitative Structure-Activity Relationship
Quinolones
Quinolones - chemistry
Quinolones - pharmacology
Thiophenes - chemistry
Thiophenes - pharmacology
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Summary: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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2010.05.014