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Synthesis, antiproliferative activity and DNA binding of amino and amido substituted pentacyclic benzimidazole derivatives

Benzimidazoles and their azino-fused derivatives are important and fundamental structural motifs in medicinal chemistry found in a variety of bioactive natural and numerous synthetic medical and biochemical agents, which possess different chemical and pharmacological features [1]. Quinoline-fused tetracyclic benzimidazoles, recently prepared and published in our research group, have shown to be a very promising class of antiproliferative agents and intercalators [2]. Importantly, due to the structural similarity of with naturally occurring nucleotides, benzimidazole derivatives can easily interact with biomolecules like DNA, RNA or proteins in living systems. DNA molecule is still one of the principal targets in anticancer drug development strategies since it has a central role in many life processes. Pentacyclic compounds were prepared by conventional reactions of organic synthesis as well as by photochemical and microwave assisted reactions [1-3]. Targeted amino substituted benzimidazole derivatives obtained in the uncatalyzed microwave assisted amination from corresponding halogeno substituted precursors, while amido substituted derivatives obtained in the reaction of corresponding pentacyclic acyl chlorides and chosen amines. All prepared compounds were tested for their antiproliferative activity in vitro on several human cancer cells. A few compounds showed very strong activity in submicromolar range of inhibitory concentrations and thus, were chosen to study their DNA binding as possible mechanism of biological action.

benzimidazole ; amination ; antiproliferative activity

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