engleski

Synthesis, antiprolifetaive activity and DNA binding studies of novel amino substituted benzimidazo[1, 2-a]quinokines

The permanent and growing interest in the synthesis of azino fused benzimidazole derivatives, as a one of the most extensively studied classes of heterocyclic compounds, is a direct consequence of their diverse biological properties. We represent the synthesis of benzimidazo[1, 2-a]quinolines with amino side chains placed on quinoline nuclei in view of our continuing search and finding of new lead structures with chemotherapeutic activities.[1, 2] Amino-substituted compounds were synthesized by uncatalyzed microwave assisted amination from chloro-substituted precursor. All compounds showed prominent antiproliferative activity, while the length of the amino chains linked to the benzimidazo[1, 2-a]quinoline nuclei manipulated the antiproliferative activity. Although the majority of compounds were active in the submircomolar IC50 concentrations, we performed a series of additional experiments to shed more light on the mechanisms of action of the most active ones, including DNA binding, topoisomerases I and II inhibition, cell cycle perturbances and cellular localization.

benzimidazo[1; 2-a]quinolines; amino substituents; antiproliferative activity; inhibition of topoisomerase I and II; fluorescence microscopy

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