广告
二氢睾酮
体内
化学
效力
还原酶
同工酶
IC50型
酶
生物化学
生物信息学
药理学
体外
立体化学
雄激素
生物
基因
生物技术
激素
作者
Kejing Lao,Jie Sun,Chong Wang,Weiting Lyu,Boshen Zhou,Ruheng Zhao,Qian Xu,You Qin,Hua Xiang
出处
期刊:Steroids
[Elsevier]
日期:2017-08-01
卷期号:124: 29-34
被引量:8
标识
DOI:10.1016/j.steroids.2017.05.011
摘要
5α-Reductase is a key enzyme responsible for dihydrotestosterone biosynthesis and has been recognized as an important target for discovering new drugs against benign prostatic hyperplasia (BPH). In this study, a series of novel steroidal androst-3,5-diene-3-carboxylic acids have been designed and synthesized. Biological evaluations were performed on their 5α-reductase inhibitory activities by both in vitro enzyme inhibition assay and in vivo by prostate weighing method. Results showed that most of them displayed excellent 5α-reductase inhibitory potency. Detailed evaluation indicated that most of the compounds displayed slightly higher inhibition potency towards type 2 isozyme. Among all the compounds, 16a was found to be the most potential inhibitor with the IC50 of 0.25 μM and 0.13 μM against type 1 and 2 isozymes respectively. In vivo 5a-reductase inhibitory evaluation of 16a also showed a more significant reduction effect (p < 0.001) in rat prostate weight than epristeride. Furthermore, the results of in silico ADME study indicated that compound 16a exhibited good pharmacokinetic properties. Thus, 16a could serve as promising lead candidates for further study.
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