title: Bioactivation of carbamate-based 20(S)-camptothecin prodrugs.
abstract: 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.
authors.affiliation: School of Chemistry, Faculty of Exact Sciences, Tel-Aviv University, Tel Aviv 69978, Israel.
authors.forename: Neta
authors.initials: N
authors.lastname: Pessah
authors.forename: Mika
authors.initials: M
authors.lastname: Reznik
authors.forename: Marina
authors.initials: M
authors.lastname: Shamis
authors.forename: Ferda
authors.initials: F
authors.lastname: Yantiri
authors.forename: Hong
authors.initials: H
authors.lastname: Xin
authors.forename: Katherine
authors.initials: K
authors.lastname: Bowdish
authors.forename: Noam
authors.initials: N
authors.lastname: Shomron
authors.forename: Gil
authors.initials: G
authors.lastname: Ast
authors.forename: Doron
authors.initials: D
authors.lastname: Shabat
mesh_terms: 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
chemical_list: D002219:Carbamates; D006131:Growth Inhibitors; D011355:Prodrugs; D002166:Camptothecin