Effect of 3,4-ethylenedioxy-extension of thiophene core on the DNA/RNA binding properties and biological activity of bisbenzimidazole amidines
| Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
|---|---|
| Data(s) |
20/10/2012
20/10/2012
2009
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| Resumo |
Novel bisbenzimidazoles (4-6), characterized by 3,4-ethylenedioxy-extension of thiophene core, revealed pronounced affinity and strong thermal stabilization effect toward ds-DNA. They interact within ds-DNA grooves as dimmers or even oligomers and agglomerate along ds-RNA. Compounds 4-6 have shown moderate to strong antiproliferative effect toward panel of eight carcinoma cell lines. Compound 5 displayed the best inhibitory potential and in equitoxic concentration (IC(50) = 1 x 10 (6) M) induced accumulation of cells in G2/M phase after 48 h of incubation. Fluorescence microscopy showed that 5 entered into live HeLa cells within 30 min, but did not accumulate in nuclei even after 2.5 h. Compound 5 inhibited the growth of Trypanosome cruzi epimastigotes (IC(50) = 4.3 x 10 (6) M). (C) 2009 Elsevier Ltd. All rights reserved. Croatian Ministry of Science, Education[053-0982914-2965] Croatian Ministry of Science, Education Croatian Ministry of Science, Education[219-0982914-2176] Croatian Ministry of Science, Education Croatian Ministry of Science, Education Croatian Ministry of Science, Education[219-0982914-2179] Croatian Ministry of Science, Education Croatian Ministry of Science, Education[098-0982914-2918] Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[03/13257-8] |
| Identificador |
BIOORGANIC & MEDICINAL CHEMISTRY, v.17, n.6, p.2544-2554, 2009 0968-0896 http://producao.usp.br/handle/BDPI/28547 10.1016/j.bmc.2009.01.071 |
| Idioma(s) |
eng |
| Publicador |
PERGAMON-ELSEVIER SCIENCE LTD |
| Relação |
Bioorganic & Medicinal Chemistry |
| Direitos |
closedAccess Copyright PERGAMON-ELSEVIER SCIENCE LTD |
| Palavras-Chave | #Benzimidazole amidine #DNA/RNA binding #Antiproliferative activity #Antiparasitic activity #DNA MINOR-GROOVE #TUMOR-CELLS #ANTITUMOR EVALUATION #AROMATIC DIAMIDINES #FURAMIDINE ANALOGS #BIS-BENZIMIDAZOLES #DERIVATIVES #AGENTS #BINDERS #COMPLEXES #Biochemistry & Molecular Biology #Chemistry, Medicinal #Chemistry, Organic |
| Tipo |
article original article publishedVersion |
