Synthesis of 2-aryl-4-(benzimidazol-2-yl)-1,2-dihydro[1,2,4]triazino-[4,5-a]benzimidazol-1-one derivatives with preferential cytotoxicity against carcinoma cell lines.
In this paper we describe the preparation of some derivatives of 1,2,4-triazino[4,5-a]benzimidazol-1-ones (5 and 6), containing additional benzimidazole ring. These compounds were prepared using coupling reactions of diazonium salts with 1,1-bis(1-ethoxycarbonyl-benzimidazol-2-yl)methane (2) to obtain unstable hydrazones 4, which readily undergo cyclization. Interestingly, the selected compounds demonstrated preferential cytotoxic activities against human carcinoma and glioma cell lines compared with leukemic cells. They showed significant activity against multidrug-resistant P-glycoprotein expressing cell lines but had less effect on multidrug-resistance protein 1 positive and topoisomerase IIalpha negative leukemias.
Stýskala
Jakub
J
Department of Organic Chemistry, Faculty of Science, Palacký University, Tr. Svobody 8, 771 46 Olomouc, Czech Republic.
Stýskalová
Libuse
L
Slouka
Jan
J
Hajdúch
Marián
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D012680:Sensitivity and Specificity
D000970:Antineoplastic Agents; D001562:Benzimidazoles