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Ï´ÍѼÁ(½ð±Ò+1): ÕªÒªÎÒϵ½ÁË£¬Ã»ÓÐÈ«Îİ¡£¡²»¹ÜÔõÑù£¬Ð»Ð»£¡ 2011-05-05 18:00:48
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Synthesis, SAR and biological evaluation of racemic abyssinone II and analogs as potential aromatase inhibitors for prevention of breast cancer.     Maiti, Arup; Cuendet, Muriel; Croy, Vicki L.; Endringer, Denise C.; Pezzuto, John M.; Cushman, Mark.    Department of Medicinal Chemistry and Molecular Pharmacology and The Purdue Cancer Center,  Purdue University,  West Lafayette,  IN,  USA.    Abstracts of Papers, 233rd ACS National Meeting, Chicago, IL, United States, March 25-29, 2007  (2007),     MEDI-093.  Publisher: American Chemical Society,  Washington, D. C  CODEN: 69JAUY  Conference; Meeting Abstract; Computer Optical Disk  written in English.    AN 2007:295526    CAPLUS  

Abstract

Aromatase, which converts androgens to estrogens and catalyzes the transformation of pro-carcinogens to carcinogenic metabolites, is an attractive target for the chemoprevention of breast cancer.  Inhibitors of aromatase show an overall superior efficacy over selective estrogen receptor modulators (SERMs), a std. therapy used in the treatment of estrogen-receptor-pos. breast cancer in postmenopausal women.  Previous studies showed that (S)-abyssinone, isolated from Broussonetia papyrifera L., is a potent aromatase inhibitor.  An efficient approach to the synthesis of racemic abyssinone II and a series of its analogs as well as their biol. evaluation as potential selective aromatase inhibitors are described.  Racemic abyssinone II showed an IC50 value of 28.0 .mu.M by fluorimetric assay.  Several novel racemic analogs displayed increased aromatase inhibitory activity relative to abyssinone II, with IC50 values starting from as low as 1.9 .mu.M.  A structure-activity (SAR) model was established to search for new potent chemopreventive agents.  This research was supported by program project grant P01 CA48112 funded by the NCI.
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