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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.
AuthorsLivio Racané, Ranko Stojković, Vesna Tralić-Kulenović, Helena Cerić, Marijana Đaković, Katja Ester, Ana Mišir Krpan, Marijana Radić Stojković
JournalEuropean journal of medicinal chemistry (Eur J Med Chem) Vol. 86 Pg. 406-19 (Oct 30 2014) ISSN: 1768-3254 [Electronic] France
PMID25194933 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Masson SAS. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Benzothiazoles
  • Mesylates
  • Polynucleotides
Topics
  • Animals
  • Antineoplastic Agents (administration & dosage, chemistry, pharmacology)
  • Benzothiazoles (chemical synthesis, chemistry, pharmacology)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HeLa Cells
  • Humans
  • MCF-7 Cells
  • Male
  • Mesylates (chemical synthesis, chemistry, pharmacology)
  • Mice
  • Mice, Inbred BALB C
  • Models, Molecular
  • Molecular Structure
  • Polynucleotides (administration & dosage, chemistry, pharmacology)
  • Structure-Activity Relationship

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