Antitumor Activity, Pharmacology, and Toxicity of Ellipticines, Ellipticinium, and 9-Hydroxy Derivatives: Preliminary Clinical Trials of 2-Methyl-9-Hydroxy Ellipticinium (NSC 264-137)

Ellipticine and some derivatives are highly cytotoxic substances which kill L1210 cells at concentrations ranging form 10-8 to 10-6 M. Some compounds in this series bind with high affinity to DNA (affinity constant between 107 M -1 and 105 M -1) by intercalation between base pairs. The antitumoral properties of these derivatives are thought to be related to their DNA-binding ability. Both 9-hydroxylation of ellipticine and quaternarization of 2-pyridinic nitrogen tend to increase DNA binding and antitumor activity.