Relative binding affinity of novel steroids to androgen receptors in hamster prostate

Abstract

The in vivo and in vitro antiandrogenic activity of four aromatic esters 10a-10d, one aliphatic ester 10e based on the pregna-4,16-diene-6, 20-dione structure and two aromatic 17c, 17d and two aliphatic valeroyloxy esters 17a, 17b based on the more saturated 4-pregnene-6,20-dione skeleton was examined. The biological activity of steroids 9, 10a-10e and 17a-17d, was determined using prostate glands from gonadectomized adult male golden hamsters. In the in vitro studies, the relative binding affinity of these steroids to cytoplasmic androgen receptor (AR) of hamster prostate was determined from, the corresponding IC50 values obtained from the competitive binding plots. The standards dihydrotestosterone (DHT) and cyproterone (CA) acetate used have displaced [3H]DHT from the AR with an IC50 value of 3.2 and 4.4 nM respectively. All steroidal compounds synthesized in this study showed a binding affinity for the androgen receptor, present in the cytosol from prostate hamster; compounds 10a-10c showed the highest affinities for this receptor. The in vivo experiments showed that all steroidal derivatives were subcutaneously active, since they decreased the weight of the prostate gland in gonadectomized hamsters treated with DHT, and are antagonists for the androgen receptor since they block the DHT-induced prostate weight gain. The derivatives having the more conjugated 4,16-pregnadiene-6, 20-dione system (10a-10c) exhibited a higher antiandrogenic activity than the corresponding steroids (17a-17d) based on the more saturated 4-pregnene-6,20-dione system.

6-Bromo-2-naphthol from Silene armeria extract sensitizes Acinetobacter baumannii strains to polymyxin

“…Linoleic and oleic acids from H. pedunculatum are known to have antimicrobial activities against only gram-positive bacteria, including S. aureus 28 . Pregna-4,16-diene-3,11,20-trione was excluded by us from further analyses because it has been proven to have higher antiandrogenic activity in the hamster prostate 29 . Of the selected candidates, 6B2N was the only promising adjuvant that was experimentally tested to have a synergistic effect with PMB (Fig.…”

Antiandrogenic and apoptotic effects of RU-486 on animal prostate

“…Tissues were homogenized in one volume of buffer TEMD plus protease inhibitors (2 mM PMSF, 10 g/ml antipain, 5 mM leupeptin [11]) in ice bath with a tissue homogenizer.…”

“…Homogenates were centrifuged at 140,000 × g for 60 min [11] in a SW 60 Ti rotor (Beckman Instruments, Palo Alto, CA).…”

Synthesis and characterization of new aromatic esters based on 4,16-pregnadiene-6,20-dione skeleton

“…Recently Cabeza and collegues synthesized a series of 3β-benzoyloxy-4,16-pregnadiene-6,20-dione ( 1a - e , Figure 1) and 3β- cycloalkylcarbonyloxy-4,16-pregnadiene-6,20-dione ( 2a - d , Figure 1) compounds starting from 16-dehydropregnenolone acetate (16-DPA) and evaluated their biological activities. Of these steroids 1a is a good inhibitor for the 5α-reductase enzyme [13] while 1b - e and 2a - d showed high antiandrogenic activity [28,29]. In continuation of our study on steroids [30,31] and to explore an improved way for synthesis of new steroidal compounds from the cheap starting material diosgenin, herein we report the synthesis and structural characterization of a series of new aromatic esters based on 4,16-pregnadiene-6,20-dione skeleton.…”