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Chalcone Derivatives Inhibit Glutathione S‐Transferase P1‐1 Activity: Insights into the Interaction Mode of α, β‐Unsaturated Carbonyl Compounds
Author(s) -
Wang Jian,
Wang Shaojie,
Song Dandan,
Zhao Dongmei,
Sha Yu,
Jiang Yuting,
Jing Yongkui,
Cheng Maosheng
Publication year - 2009
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2009.00807.x
Subject(s) - chalcone , glutathione , glutathione s transferase , transferase , chemistry , biochemistry , pharmacology , stereochemistry , enzyme , biology
Resistance to chemotherapeutic drugs has long been a considerable barrier to successful treatment of many cancers and over‐expression of glutathione S‐transferase P1‐1 is correlated to carcinogenesis and resistance of cancer cells against chemotherapeutic agents. This study throws light on the role of chalcone derivatives, a new class of glutathione S‐transferase P1‐1 inhibitors potentially to overcome glutathione S‐transferase P1‐1‐mediated chemotherapy resistance. Nineteen α‐substituted chalcone derivatives were synthesized and their in vitro inhibitory effects on glutathione S‐transferase P1‐1 were determined. We interestingly found that most of these compounds showed inhibitory effect on glutathione S‐transferase P1‐1 activity. In addition, molecular field‐based similarity analysis provides the necessary three‐dimensional molecular field properties of α, β‐unsaturated carbonyl derivatives to inhibit glutathione S‐transferase P1‐1 activity. Thus, these compounds have great potential to be developed into novel chemotherapeutic sensitizers.