ABSTRACT
Camptothecin (CPT) (1) (Figure 2.1) is a naturally occurring alkaloid isolated from the bark of Camptotheca acuminata, a tree native to central China. The beginning of interest in C. acuminata extracts was in the 1950s; the structure of CPT was determined by x-ray crystallography as a pentacyclic alkaloid and was disclosed in 1966.1 In addition to its structural novelty, CPT received much attention due to its striking activity in in vivo L1210 mouse life-prolongation assays and in vitro 9KB cytotoxicity assays.2 Clinical evaluations were pursued with the water-soluble sodium salt (2), which unfortunately yielded only modest results and an unmanageable number of side-effects.3 In 1985, Hsiang et al. reported that topoisomerase I (topo I) was the cellular target of CPT and thereby renewed interest in its study and clinical advancement.4 At present, CPT remains one of the most widely investigated natural products and three analogs of CPT have been approved for clinical use in selected cancer indications (i.e., topotecan-Hycamtin, 3; irinotecanCamptosar, 4; and CKD-602-belotecan, 5). This chapter serves as a summary of the mechanism of action, biological scope, synthetic studies and structure-activity relationships (SARs), and developing clinical applications of CPT and is intended to complement our earlier chapter covering this important natural product.
