For selective cancer chemotherapy, we previously designed and synthesized two β-glucuronidase-activated prodrugs of camptothecin (9-ACG and 10-HCG), which increased water solubility for camptothecins. In normal tissues, β-glucuronidase is localized primarily in lysosomes and thereby not available for activation of glucuronide prodrugs because these prodrugs are generally hydrophilic, thus rendering them impermeable to cell membranes. Therefore, glucuronide-based prodrugs can be used in prodrug monotherapy.9-ACG was more soluble than 10-HCG via oxycarbamate linkage, so 9-ACG was more low toxicity than 10-HCG. However, 10-HCG was a good substrate for β-glucuronidase, which has ether linkage. In order to increase the solubility of 10-HCG, we designed 10-HCPG, which creates a hydrophilic group in link of prodrug. We predict that 10-HCPG is soluble, low cytotoxicity and good a substrate for β-glucuronidase. We expect 10-HCPG, which is a good candidate for selective cancer chemotherapy.
