Chemistry and biology of camptothecin and its derivatives

Authors:

• Karol Kacprzak

Abstract

Quinoline alkaloid camptothecin (CPT) isolated in 1958 from Chinese tree Camptotheca acuminata is an important natural product serving as a lead compound for designing many more active and clinically useful anticancer drugs, such as approved topotecan and irinotecan. All camptothecins exhibit a unique mechanism of action involving inhibition of topoisomerase I which leads to the interruption of cell division processes. Current efforts in CPT research focus on construction of better drugs, prodrugs, and new forms of administration. Important area of clinical work involves testing of multidrug regimens of CPTs with conjunction of other anticancer drugs. This often resulted in an improved activity toward malignancies. Beside anticancer activity, camptothecin and related compounds display also other activities such as antiviral or antiprotozoal. Insufficient natural supply of camptothecin led to significant improvement of camptothecins total synthesis as well as to attempts of its biotechnological production. The present chapter covering over 300 references is intended to provide a complete but condensed overview on camptothecins, with emphasis on the newest work in the field.