Spectrophotometric and Voltammetric Studies on the Interaction of 7-Ethyl-10- hydroxycamptothecin (SN-38) as the Metabolized Compound of CPT-11 with ds-DNA

Camptothecin is a natural, water-insoluble alkaloid produced by two Asian trees, Camptotheca acuminata and Mappia foetida. In the 1970s, preliminary clinical trials with camptothecin demonstrated promising antitumor activity, for example, in gastric cancer. Unfortunately, there were also severe side effects, including poorly predictable hemorrhagic cystitis, gastrointestinal toxicities and myelosuppression. It was not until the early 1980s that the mechanism of antitumor activity of camptothecin was identified as the inhibition of topoisomerase I. Researchers then began to modify camptothecin and created a host of analogues with the aim of overcoming the two key factors that hampered clinical application of the parent drug: poor water-solubility and severe toxicity. A number of camptothecin analogues are currently at different stages of clinical development, including topotecan (TPT), irinotecan (CPT-11), lurtotecan (LRT), 9aminocamptothecin (9-AC), 10-hydroxycamptothecin (SN-38) and 9-nitrocamptothecin (9-NC). Thus far, most clinical experience relates to the water-soluble derivatives topotecan and irinotecan. Irinotecan is converted in vivo to its much higher active metabolite, 7-ethyl-10-hydroxy camptothecin (SN-38) by carboxylesterases. Its disposition by the liver and bile is higher than by any other tissue. Spectrophotometric and Voltammetric Studies on the Interaction of 7-Ethyl-10hydroxycamptothecin (SN-38) as the Metabolized Compound of CPT-11 with ds-DNA