engleski

Novel Substituted Benzothiophene and Thienothiophene Carboxanilides and Quinolones: Synthesis, Photochemical Synthesis, DNA-Binding Properties, Antitumor Evaluation and 3D-Derived QSAR Analysis

A series of new N, N-dimethylaminopropyl- and 2-imidazolinyl-substituted derivatives of benzo[b]thienyl- and thieno[2, 3-b]thienyl-carboxanilides and benzo[b]thieno[2, 3-c]- and thieno[3’, 2’:4, 5]thieno[2, 3-c]quinolones were prepared. Quinolones were prepared by the reaction of photochemical dehydrohalogenation of corresponding anilides. Carboxanilides and quinolones were tested for the antiproliferative activity. 2-Imidazolinyl-substituted derivatives showed very prominent activity. Using the experimentally obtained antitumor measurements, 3D-derived QSAR analysis was performed for the set of compounds. Higly predicitive 3D-derived QSAR models were obtained and molecular properties that have the highest impact on antitumor activity were identified. Carboxanilides 6a-c and quinolones 9a-c and 11a were evaluated for DNA binding propensities and topoisomerases I and II inhibition as part of their mechanism of action assessment. The evaluated differences in the mode of action nicely correlate with the results of the 3D- QSAR analysis. Taken together the results indicate which modifications of the compounds from the series should further improve their anticancer properties.

substituted benzothiophene- ; thienothiophene-carboxanilides ; quinolones ; antitumor evluation ; QSAR analysis ; DNA-binding

Na radu su radili i suradnici u okviru bilateralne suradnje Hubert Curien između Hrvatske i Francuske institucije u okviru Cogito programa kao Egide project N°24765PH. M-H.D.-C.