期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 86, 期 -, 页码 406-419出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2014.08.072
关键词
Amino-amidino disubstituted 2-phenylbenzothiazoles; DNA/RNA; Intercalation; Minor groove binding; Antiproliferative activity
资金
- Ministry of Science, Education and Sport of Croatia [098-0982914-2918, 098-0982464-2514, 119-1193079-1332, 098-0982464-2390, 117-0000000-3283]
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. (C) 2014 Elsevier Masson SAS. All rights reserved.
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