ABSTRACT
Camptothecin is a planar pentacyclic alkaloid containing a pyrrolo(3,4-β)quinoline and an α-hydroxy lactone, discovered in the early 1960s from the stem wood of Camptotheca acuminata, Decne (family Nyssaceae). Despite its promising and broad-spectrum anticancer potential, its initial application was restricted due to its poor water solubility of the lactone form, its inactivation at physiological pH, and the severe toxicity of its carboxylate form. In the late 1980s, the DNA topoisomerase I enzyme was discovered to be the therapeutic target for CPT, placing it at the forefront of research on anticancer drugs. The high-yield chemical synthesis of CPT further created an upsurge in scientific interest, leading to the development of several derivatives with improved pharmacodynamic and pharmacokinetic properties. The derivatives like topotecan, irinotecan, and belotecan were approved by the authorities as chemotherapeutic drugs. Today, a number of new-generation CPT derivatives with improved pharmacological properties are at various stages of preclinical and clinical trials. This chapter reviews the synthetic and semisynthetic approaches that led to the development of CPT and its derivatives and provides an update pertaining to its pharmacodynamic and pharmacokinetic properties.
