Antitumor Carbazoles

Christian      Asche; Martine      Demeunynck

Abstract

Natural and synthetic carbazoles, either in a pure substituted or in an annellated substituted form, represent an important and heterogeneous class of anticancer agents, which has grown considerably over the last two decades. Many carbazole derivatives have been tested for cyctotoxic activity, some of them have entered clinical trials, but only very few have been approved for the treatment of cancer so far, since the clinical application of many carbazoles has encountered problems like severe side effects or multidrug resistance. Due to their polycyclic, planar and aromatic structure carbazoles are predestined for intercalation into DNA and therefore DNA remains one of the main targets for cytotoxic carbazoles. For many carbazoles cytotoxicity can be related to DNA-dependent enzyme inhibition such as topoisomerase I/II and telomerase. But also other targets such as cyclin-dependent kinases and estrogen receptors have emerged.

Keywords: Antitumor agents, DNA binder, nitrogen heterocycles, DNA intercalation, topoisomerase inhibition

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