The anti- and pro-oxidant effects of green tea catechins have been implicated in the alterations of cellular functions determining their chemoprotective and therapeutic potentials in toxicity and diseases. The glutathione S-transferases (GSTs; EC 2.5.1.18) family is a widely distributed phase-II detoxifying enzymes and the GST P1-1 isoenzyme has been shown to catalyze the conjugation of GSH with some alkylating anti-cancer agents, suggesting that over-expression of GST P1-1 would result in tumor cell resistance. Here we report the docking study of four green tea catechins and four alkylating anticancer drugs into the GST P1-1 model, as GSTs were found to be affected by tea catechins. The EGCG ligands exhibit higher docking potential with respect to the anticancer agents, with a ligand-receptor interaction pattern indicating an high conformational stability. Consequently, the competition mechanisms favourable for the green tea catechins could lead to enzyme(s) desensitisation with a reduction of the alkylating drugs metabolism. The results provide a useful theoretical contribution in understanding the biochemical mechanisms implicated in the chemotherapeutic use of green tea catechins in oxidative stress-related diseases.

Green tea catechins in chemoprevention of cancer: A molecular docking investigation into their interaction with glutathione S-transferase (GST P1-1) / R. Artali, G. Beretta, P. Morazzoni, E. Bombardelli, F. Meneghetti. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - 24:1(2009), pp. 287-295. [10.1080/14756360802177282]

Green tea catechins in chemoprevention of cancer: A molecular docking investigation into their interaction with glutathione S-transferase (GST P1-1)

R. Artali
Primo
;
G. Beretta
Secondo
;
F. Meneghetti
Ultimo
2009

Abstract

The anti- and pro-oxidant effects of green tea catechins have been implicated in the alterations of cellular functions determining their chemoprotective and therapeutic potentials in toxicity and diseases. The glutathione S-transferases (GSTs; EC 2.5.1.18) family is a widely distributed phase-II detoxifying enzymes and the GST P1-1 isoenzyme has been shown to catalyze the conjugation of GSH with some alkylating anti-cancer agents, suggesting that over-expression of GST P1-1 would result in tumor cell resistance. Here we report the docking study of four green tea catechins and four alkylating anticancer drugs into the GST P1-1 model, as GSTs were found to be affected by tea catechins. The EGCG ligands exhibit higher docking potential with respect to the anticancer agents, with a ligand-receptor interaction pattern indicating an high conformational stability. Consequently, the competition mechanisms favourable for the green tea catechins could lead to enzyme(s) desensitisation with a reduction of the alkylating drugs metabolism. The results provide a useful theoretical contribution in understanding the biochemical mechanisms implicated in the chemotherapeutic use of green tea catechins in oxidative stress-related diseases.
Alkylating anti-cancer drugs; EC 2.5.1.18); Epigallocatechingallate; Glutathione S-transferases (GSTs; Green tea chemoprevention; Molecular docking; Phase-II detoxifying enzymes
Settore CHIM/08 - Chimica Farmaceutica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/55253
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