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.
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Authors | Livio Racané, Ranko Stojković, Vesna Tralić-Kulenović, Helena Cerić, Marijana Đaković, Katja Ester, Ana Mišir Krpan, Marijana Radić Stojković |
Journal | European journal of medicinal chemistry
(Eur J Med Chem)
Vol. 86
Pg. 406-19
(Oct 30 2014)
ISSN: 1768-3254 [Electronic] France |
PMID | 25194933
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Benzothiazoles
- Mesylates
- Polynucleotides
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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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