Background: Camptothecin (CPT), a pentacyclic alkaloid isolated by Wall et al. in 1958 from the Chinese tree Camptotheca acuminata, was reported to possess an interesting antitumor activity. Late in 1985, it was reported by Liu et al. that the cytotoxic activity of CPT was attributed to a novel mechanism of action involving the nuclear enzyme classified as type I DNA topoisomerase. Since the explanation of the unique mechanism of action, many derivatives have been synthesized and some of them are in various stages of preclinical and clinical development. Among them, two derivatives, topotecan and irinotecan, have successfully entered into the market and are used as topoisomerase I poisons in clinical practice.
Objective: The main focus of the present review is to describe the development of CPT derivatives over the years dividing them by decades according to the date of discovery and focusing attention on molecules that were published in patents.
Results/conclusion: To summarize, > 150 patents have been deposited over the past 30 years. Structure-activity relationship studies suggest that substitutions at the 7-, 9- or 10-positions of most CPT derivatives enhance their antitumor activity, but at the 11- or 5-position usually lead to activity decrease.