Effect of 3,4-ethylenedioxy-extension of thiophene core on the DNA/RNA binding properties and biological activity of bisbenzimidazole amidines

Autor(es)

Stolic, Ivana ^[1] ; Miskovic, Katarina ^[2] ; Magdaleno, Anahi ^[3] ; Silber, Ariel Mariano ^[3] ; Piantanida, Ivo ^[4] ; Bajic, Miroslav ^[1] ; Glavas-Obrovac, Ljubica ^[2]

Afiliação do(s) autor(es)

^[1] Univ Zagreb, Dept Chem & Biochem, Fac Vet Med, Zagreb 10000 - Croatia

^[2] JJ Strossmayer Univ Osijek, Dept Med Chem & Biochem, Sch Med, Osijek 31000 - Croatia

^[3] Univ Sao Paulo, Dept Parasitol, Inst Biomed Sci, Sao Paulo - Brazil

^[4] Rudjer Boskovic Inst, Div Organ Chem & Biochem, Zagreb - Croatia

• Tipo de documento: Artigo Científico
• Fonte: Bioorganic & Medicinal Chemistry; v. 17, n. 6, p. 2544-2554, MAR 15 2009.
• Citações Web of Science: 25

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. (AU)

• Processo FAPESP: 03/13257-8 - Clonagem e caracterização de transportadores de aminoácidos em Trypanosoma cruzi: uma abordagem pós-genômica
• Beneficiário: Ariel Mariano Silber
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores