1. Synthesis and Evaluation of Benzoxazolinonic Imidazoles and Derivatives as Non-steroidal Aromatase Inhibitors.
- Author
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Nativelle-Serpentini, Celine, Moslemi, Safa, Yous, Said, Park, Chang Ha, Lesieur, Daniel, Sourdaine, Pascal, and Séralini, Gilles-Eric
- Subjects
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CYTOCHROMES , *HEMOPROTEINS , *AROMATASE , *ESTROGEN , *CHEMISTRY - Abstract
New compounds were tested in vitro on aromatase activity in human placental and equine testicular microsomes. Equine aromatase, very well characterized biochemically, is used as a comparative model to understand the mechanism of aromatase inhibition. Among 15 molecules screened, 5 of them ( 11 - 15 ) strongly inhibit human and equine aromatases with IC 50 values ranging from 13-85 nM and from 23-103 nM respectively. These results were corroborated by K i / K m values. Moreover, spectral studies showed a type II spectrum with both enzymes, which is characteristic of an interaction between the nitrogen atom of the molecule and the heme of the cytochrome P450. Compound 12 , which has the lowest IC 50 and K i / K m ratio, inactivates aromatase in a dose and time-dependent manner. This might be very important for the treatment of estrogen-dependent diseases such as breast cancer. Finally, MTT assays on E293 cells revealed that the molecules were not cytotoxic. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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