title: Interactions with polynucleotides and antitumor activity of amidino and imidazolinyl substituted 2-phenylbenzothiazole mesylates.
abstract: Based on previously reported antiproliferative activity screening, four most promising disubstituted 2-phenylbenzothiazole hydrochlorides were chosen for detailed study. Water solubility, as well as liphophilicity/hydrophilicity balance of organic core were modified by conversion to mesylate salts. For purpose of structure/activity studies their structures were determined by X-ray structure analysis. Detailed analysis of interactions of new compounds with double stranded (ds-) DNA/RNA by UV/Vis and CD titrations, thermal melting and viscometry experiments revealed that most of studied compounds intercalate into ds-RNA but bind into minor groove of AT-DNA, and agglomerate along GC-DNA. Furthermore, compounds also interact with ss-RNA, but only amino-imidazolinyl 2-phenylbenzothiazole, 4b displayed well defined orientation and dominant binding mode (by induced CD signals) with poly A and poly G. Besides, in vitro investigations revealed moderate to high antiproliferative activity of benzothiazoles against seven human cancer cell lines, while in some cases (HTC 116, SW620, MIA PaCa-2) high correlation between the type of the amidino group and cytotoxic activity was observed.
authors.affiliation: Department of Applied Chemistry, Faculty of Textile Technology, University of Zagreb, Prilaz baruna Filipovića 28a, 10000 Zagreb, Croatia.
authors.forename: Livio
authors.initials: L
authors.lastname: Racané
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, PO Box 180, 10002 Zagreb, Croatia.
authors.forename: Ranko
authors.initials: R
authors.lastname: Stojković
authors.affiliation: Department of Applied Chemistry, Faculty of Textile Technology, University of Zagreb, Prilaz baruna Filipovića 28a, 10000 Zagreb, Croatia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Tralić-Kulenović
authors.affiliation: Pliva Croatia Ltd., TAPI Research & Development, Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia.
authors.forename: Helena
authors.initials: H
authors.lastname: Cerić
authors.affiliation: Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia.
authors.forename: Marijana
authors.initials: M
authors.lastname: Đaković
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, PO Box 180, 10002 Zagreb, Croatia.
authors.forename: Katja
authors.initials: K
authors.lastname: Ester
authors.affiliation: Department of Oncology, KBC Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia.
authors.forename: Ana Mišir
authors.initials: AM
authors.lastname: Krpan
authors.affiliation: Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, PO Box 180, HR-10002 Zagreb, Croatia. Electronic address: mradic@irb.hr.
authors.forename: Marijana Radić
authors.initials: MR
authors.lastname: Stojković
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D008698:Mesylates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D015394:Molecular Structure; D011119:Polynucleotides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; D008698:Mesylates; D011119:Polynucleotides
keywords: Amino-amidino disubstituted 2-phenylbenzothiazoles; Antiproliferative activity; DNA/RNA; Intercalation; Minor groove binding