Chemoprotective and toxic potentials of synthetic and natural chalcones and dihydrochalcones in vitro
| Authors | |
|---|---|
| Year of publication | 2005 |
| Type | Article in Periodical |
| Magazine / Source | Toxicology |
| MU Faculty or unit | |
| Citation | |
| Web | http://www.sciencedirect.com/science?_ob=JournalURL&_cdi=5175&_auth=y&_acct=C000045159&_version=1&_urlVersion=0&_userid=835458&md5=160d52ffea677d79bea5f26abc26f23c |
| Field | Pharmacology and pharmaceutical chemistry |
| Keywords | chalcone; dihydrochalcone; toxic; chemoprotective; in vitro |
| Description | Cytochrome P4501A activity, oxidative stress and inhibition of gap junctional intercellular communication (GJIC) are involved in metabolic activation of promutagens and tumor-promoting activity of various xenobiotics, and their prevention is considered to be an important characteristic of chemoprotective compounds. In this study, a series of 31 chalcones and their corresponding dihydroderivatives, substituted in 2,2_-, 3,3_-, 4- or 4_-position by hydroxyl or methoxy group, were tested for their ability to inhibit Fe(II)/NADPH-enhanced lipid peroxidation and cytochrome P4501A-dependent 7-cethoxyresorufin-O-deethylase (EROD) activity in rat hepatic microsomes. Effects of the compounds on GJIC were determined in rat liver epithelial WBF344 cells. Most of the chalcones and dihydrochalcones inhibited EROD activity in a dose-dependent manner at the range 0.2525_M, which was comparable to model flavonoid inhibitors _-naphthoflavone and quercetin. The chalcones exhibited higher inhibition activity than the corresponding dihydroderivatives. Mono and dihydroxylated chalcones, and dihydrochalcones showed none or only a weak antioxidant activity; trihydroxyderivatives inhibited in vitro lipid peroxidation significantly only at 50_M concentration. Potential adverse effects, namely inhibition of GJIC and/or cytotoxicity were detected after treatment of WB-F344 cells with a number of chalcone and dihydrochalcone derivatives, suggesting that they should be excluded from additional screening as chemoprotective compounds. Chalcones and dihydrochalcones substituted at 4- and/or 4_-position, which elicited no inhibition of GJIC, were further tested for the potential enhancing effects on GJIC. |
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