Department of Pharmacy, Faculty of Chemistry, National University of Mexico City , Mexico, D. F. , Mexico.
J Enzyme Inhib Med Chem. 2013 Dec;28(6):1247-54. doi: 10.3109/14756366.2012.729827. Epub 2012 Oct 10.
The aim of these studies was to synthesize twelve ester derivatives of dehydroepiandrosterone with therapeutic potential. The effect of 1-12 was demonstrated in the flank organs of gonadectomized hamsters treated with testosterone and the synthesized steroids. In vitro studies were carried out determining the IC50 values for the inhibition of the activity of 5α-reductase type 1 and 2, which are present in rat liver and human prostate respectively. The binding of 1-12 to the androgen receptors (AR) was determined using rat's prostate cytosol. Steroids 1-12 containing different substituents in the phenyl group of the ester moiety in C-3 reduced the flank organs and inhibited the activity of 5α-R type 1; however only steroids 1 and 2 inhibited 5α-R type 2. 1-12 did not bind to the AR. The modification of one atom of the substituents in the phenyl group of the ester moiety in C-3 changed their biological potency (IC50).
这些研究的目的是合成具有治疗潜力的十二种脱氢表雄酮酯衍生物。研究了 1-12 对用睾酮和合成类固醇处理的去势仓鼠侧翼器官的影响。进行了体外研究，确定了对 5α-还原酶 1 型和 2 型活性抑制的 IC50 值，这两种酶分别存在于大鼠肝脏和人前列腺中。使用大鼠前列腺细胞质确定了 1-12 与雄激素受体（AR）的结合。含有酯部分 C-3 中苯环上不同取代基的类固醇 1-12 减少了侧翼器官并抑制了 5α-R 型 1 的活性；然而，只有类固醇 1 和 2 抑制了 5α-R 型 2。1-12 不与 AR 结合。酯部分 C-3 中苯环上取代基的一个原子的修饰改变了它们的生物学效力（IC50）。
