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Journal Article
Research Support, Non-U.S. Gov't
Design, synthesis and antiproliferative effect of 17β-amide derivatives of 2-methoxyestradiol and their studies on pharmacokinetics.
Steroids 2017 December
A series of 17β-amide-2-methoxyestradiol compounds were synthesized with an aim to enhance the antiproliferative effect of 2-methoxyestradiol. The antiproliferative activity of 2-methoxyestradiol analogs against human cancer cells was investigated. 2-methoxy-3-benzyloxy-17β-chloroacetamide-1,3,5(10)-triene (5e) and 2-methoxy-3-hydroxy-17β-butyramide-1,3,5(10)-triene (6c) had comparable or better antitumor activity than 2-methoxyestradiol. The elimination half-life of 6c (t1/2β =240.93min) is ten times longer than 2-ME and the area under the curve was seven times (AUC0-tmin =2068.20±315.74μgmL-1 min) higher than 2-ME, respectively. Whereas 5e had similar pharmacokinetic behavior with 2-ME (t1/2β =22.28min) with a t1/2β of 29.5 min. 6c had higher blood concentration, longer actuation duration and better suppression rate against S180 mouse ascites tumor than 2-methoxyestradiol.
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