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

Neta Pessah; Mika Reznik; Marina Shamis; Ferda Yantiri; Hong Xin; Katherine Bowdish; Noam Shomron; Gil Ast; Doron Shabat

doi:10.1016/j.bmc.2004.01.039

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

Neta Pessah, Mika Reznik, Marina Shamis, Ferda Yantiri, Hong Xin, Katherine Bowdish, Noam Shomron, Gil Ast, Doron Shabat

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1859-1866
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	12
Issue number	8
DOIs	https://doi.org/10.1016/j.bmc.2004.01.039
State	Published - 15 Apr 2004

Keywords

ADEPT
Enzymes
Prodrug Activation
Selective Chemotherapy

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10.1016/j.bmc.2004.01.039

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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.",

keywords = "ADEPT, Enzymes, Prodrug Activation, Selective Chemotherapy",

author = "Neta Pessah and Mika Reznik and Marina Shamis and Ferda Yantiri and Hong Xin and Katherine Bowdish and Noam Shomron and Gil Ast and Doron Shabat",

note = "Funding Information: This work was supported by a grant from Reckanati Foundation to GA and DS, and in part by the Israel Science Foundation to GA.",

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AU - Pessah, Neta

AU - Reznik, Mika

AU - Shamis, Marina

AU - Yantiri, Ferda

AU - Xin, Hong

AU - Bowdish, Katherine

AU - Shomron, Noam

AU - Ast, Gil

AU - Shabat, Doron

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Y1 - 2004/4/15

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AB - 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.

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

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Keywords

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