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.
Pessah
Neta
N
School of Chemistry, Faculty of Exact Sciences, Tel-Aviv University, Tel Aviv 69978, Israel.
Reznik
Mika
M
Shamis
Marina
M
Yantiri
Ferda
F
Xin
Hong
H
Bowdish
Katherine
K
Shomron
Noam
N
Ast
Gil
G
Shabat
Doron
D
D001711:Biotransformation; D002166:Camptothecin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002219:Carbamates / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
D002219:Carbamates; D006131:Growth Inhibitors; D011355:Prodrugs; D002166:Camptothecin