Novel prodrugs which are activated to cytotoxic alkylating agents by carboxypeptidase G2.
J Med Chem
; 33(2): 677-81, 1990 Feb.
Article
en En
| MEDLINE
| ID: mdl-2299634
The synthesis of three novel prodrugs, 4-[bis[2-(mesyloxy)ethyl]amino]benzoyl-L-glutamic acid (7), 4-[(2-chloroethyl)[2-(mesyloxy)ethyl]amino]benzoyl-L-glutamic acid (8), and 4-[bis(2-chloroethyl)amino]benzoyl-L-glutamic acid (9), for use as anticancer agents, is described here. Each is a bifunctional alkylating agent in which the activating effect of the ionized carboxyl function is masked through an amide bond to the glutamic acid residue. These relatively inactive prodrugs are designed to be activated to their corresponding nitrogen alkylating agents (10, 11, and 12, respectively) at a tumor site by prior administration of a monoclonal antibody conjugated to the bacterial enzyme carboxypeptidase G2 (CPG2). The viability of two different tumor cell lines was monitored with each prodrug in the presence of CPG2. All three compounds showed substantial prodrug activity--with conversion to the corresponding active drug leading to greatly increased cytotoxicity.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cisteína Endopeptidasas
/
Profármacos
/
Gamma-Glutamil Hidrolasa
/
Alquilantes
Límite:
Humans
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1990
Tipo del documento:
Article
País de afiliación:
Reino Unido
Pais de publicación:
Estados Unidos