Molecular modeling, synthesis, and preliminary biological evaluation of glutathione-S-transferase inhibitors as potential therapeutic agents.
Changes in the GSH/GST system have been found to correlate with resistance to anticancer alkylating agents, presumably through accelerated detoxification of these drugs since some GSTs have been shown to catalyze the conjugation of GSH to specific antineoplastic agents. GSH-alkyl derivatives were designed by molecular modeling, synthesized, and tested as inhibitors of human GST-Pi.
Procopio
Antonio
A
Dipartimento di Scienze Farmaco-Biologiche, Università della Magna Graecia, Complesso Ninì Barbieri, 88021 Roccelletta di Borgia (Cz), Italy. procopio@unicz.it
Alcaro
Stefano
S
Cundari
Sante
S
De Nino
Antonio
A
Ortuso
Francesco
F
Sacchetta
Paolo
P
Pennelli
Alfonso
A
Sindona
Giovanni
G
D020134:Catalytic Domain; D005027:Ethylene Oxide / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D005978:Glutathione / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship
D005982:Glutathione Transferase; D005978:Glutathione; D005027:Ethylene Oxide