Indoloquinolines as DNA binding ligands

Abstract

Indoloquinoline alkaloids isolated from natural sources are known for their broad spectrum of biological activities. The cytotoxic action of some derivatives is thought to arise from their interaction with genomic DNA driven by favorable stacking interactions of the intercalated indoloquinoline skeleton with the DNA base pairs. In addition to double-helical DNA, indoloquinoline derivatives have also been found to bind DNA triplexes as well as G-quadruplexes with high affinity, opening interesting perspectives towards the development of indoloquinoline-based DNA binding ligands with numerous potential applications in therapeutics, diagnostics and microbiology. The present paper presents an overview of studies dealing primarily with the binding of indoloquinoline analogs to double-helical, triple-helical or quadruplex targets. Available thermodynamic and structural data that also include few experimentally determined three-dimensional structures of DNA-drug complexes highlight key elements for an improved binding affinity but also important structural aspects for the design of structure-selective analogs, prerequisite for many potential applications. © 2013 Walter de Gruyter GmbH, Berlin/Boston.