Plant antitumor agents

Camptothecin (CA), an alkaloid with a peculiar anticancer mechanism, acts with a unique mechanism of action, targeting the nuclear enzyme topoisomerase I (Yang et al., 1999). CA inhibits the growth of a wide range of tumors (Giovanella et al., 1991, 1989; Potmesil, 1994). The interaction between CA and topoisomerase I was thought to occur through the attack of a nucleophilic site on the enzyme at the acyl position in the lactone of the CA structure, which plays an important role in its biological activity (Potmesil, 1994). The opening of the lactone under alkaline conditions to form the acid salt or carboxylate species results in loss of in vitro activity and apparently decreases the in vivo anticancer activity. The poor water solubility of the lactone form, instability in biological pH values and low biological activity, and the severe toxicity of the carboxylate form precluded the use of CA in clinical applications.