title: Novel substituted benzothiophene and thienothiophene carboxanilides and quinolones: synthesis, photochemical synthesis, DNA-binding properties, antitumor evaluation and 3D-derived QSAR analysis.
abstract: A series of new N,N-dimethylaminopropyl- and 2-imidazolinyl-substituted derivatives of benzo[b]thienyl- and thieno[2,3-b]thienylcarboxanilides 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. By use of the experimentally obtained antitumor measurements, 3D-derived QSAR analysis was performed for the set of compounds. Highly predictive 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.
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, P.O. Box 177, HR-10000 Zagreb, Croatia.
authors.forename: Maja
authors.initials: M
authors.lastname: Aleksić
authors.forename: Branimir
authors.initials: B
authors.lastname: Bertoša
authors.forename: Raja
authors.initials: R
authors.lastname: Nhili
authors.forename: Lidija
authors.initials: L
authors.lastname: Uzelac
authors.forename: Ivana
authors.initials: I
authors.lastname: Jarak
authors.forename: Sabine
authors.initials: S
authors.lastname: Depauw
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: David-Cordonnier
authors.forename: Marijeta
authors.initials: M
authors.lastname: Kralj
authors.forename: Sanja
authors.initials: S
authors.lastname: Tomić
authors.forename: Grace
authors.initials: G
authors.lastname: Karminski-Zamola
mesh_terms: D000813:Anilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009691:Nucleic Acid Denaturation; D055668:Photochemical Processes; D025341:Principal Component Analysis; D021281:Quantitative Structure-Activity Relationship; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D015363:Quinolones; D013876:Thiophenes; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004247:DNA