Synthesis of 11H-Pyridocarbazoles and Derivatives. Comparison of Their DNA Binding and Antitumor Activity with THose of 6H- and 7H-Pyridocarbazoles

Article abstract of DOI:10.1021/jm00159a028

The 8-methoxy- and 8-hydroxy-11H-pyrido<2,3-a>-, -<3,4-a>-, -<4,3-a>-, and <3,2-a>carbazoles were synthetized as potential DNA intercalating antitumor drugs.The structure of these compounds was confirmed by 1H NMR study including NOE experiments.The DNA binding properties of substituted and unsubstituted (8-H) heterocycles were determined by using their hydrochlorides or methiodides.These derivatives are able to bind to DNA with on affinity varying from 2.0 * 10⁴ to 1.0 * 10⁶ M^-1, but most of them are unable to intercalate in contrast with the behavior of 6H- and 7H-pyridocarbazole analogues.The cytotoxicity of 11H-pyridocarbazoles, measured on L1210 cells in vitro, is much lower than those of 6H- and 7H-pyridocarbazole analogues.