synthesis and screening of aromatase inhibitory activity of substituted c19 steroidal 17-oxime analogs合成和筛选芳香化酶抑制活性的取代c19甾族的17-oxime类似物.pdf

Molecules 2011, 16, 9868-9885; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis and Screening of Aromatase Inhibitory Activity of Substituted C19 Steroidal 17-Oxime Analogs Muna Pokhrel and Eunsook Ma * College of Pharmacy, Catholic University of Daegu, Hayang, 712-702, Korea * Author to whom correspondence should be addressed; E-Mail: masook@cu.ac.kr; Tel.: +82-53-850-3621; Fax: +82-53-850-3602. Received: 7 October 2011; in revised form: 5 November 2011 / Accepted: 7 November 2011 / Published: 28 November 2011 Abstract: The synthesis and aromatase inhibitory activity of androst-4-en-, androst-5-en-, 1β,2β-epoxy- and/or androsta-4,6-dien-, 4β,5β-epoxyandrostane-, and 4-substituted androst- 4-en-17-oxime derivatives are described. Inhibition activity of synthesized compounds was 3 assessed using aromatase enzyme and [1β- H]androstenedione as substrate. Most of the compounds displayed similar to or more aromatase inhibitory activity than formestane (74.2%). 4-Chloro-3β-hydroxy-4-androsten-17-one oxime (14, 93.8%) showed the highest activity, while 4-azido-3β-hydroxy-4-androsten-17-one oxime (17, 32.8%) showed the lowest inhibitory activity for aromatase. Keywords: aromatase inhibitor; breast cancer; conjugated androstadiene-17-oxime; 4-substituted androstene-17-oxime 1. Introduction Breast cancer is the most common c