Bioactivation of carbamate-based 20(S)-camptothecin prodrugs

Two new prodrugs of CPT were synthesized, based on carbamate linkages between the 20-hydroxy group of CPT and a linker designed to be enzymatically removed by either Penicillin-G-Amidase or catalytic antibody 38C2. Cell growth inhibition assays showed an up-to-2250-fold difference in toxicity between the prodrugs and the active drug. A significant increase in toxicity was observed upon incubation of the enzyme or the catalytic antibody with the corresponding prodrug The described derivatives of CPT further our knowledge in the design of prodrugs for use in selective approaches for targeted chemotherapy. (C) 2004 Elsevier Ltd. All rights reserved.