Effect of 3,4-ethylenedioxy-extension of thiophene core on the DNA/RNA binding properties and biological activity of bisbenzimidazole amidines.
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 2.5h. Compound 5 inhibited the growth of Trypanosome cruzi epimastigotes (IC(50)=4.3 x 10(-6)M).
Stolić
Ivana
I
Department of Chemistry and Biochemistry, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, 10000 Zagreb, Croatia.
Misković
Katarina
K
Magdaleno
Anahi
A
Silber
Ariel Mariano
AM
Piantanida
Ivo
I
Bajić
Miroslav
M
Glavas-Obrovac
Ljubica
L
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001562:Benzimidazoles / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D004996:Ethidium / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008856:Microscopy, Fluorescence; D009691:Nucleic Acid Denaturation; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013876:Thiophenes / Q000737:chemistry / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000254:growth & development
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D013876:Thiophenes; D012313:RNA; D004247:DNA; D004996:Ethidium