Determination of Rat 5α-Reductase Type 1 Isozyme Activity and Its Inhibition by Novel Steroidal Oxazolines
The 5α-reductase type 1 isozyme is a key enzyme in the metabolism of the androgen steroid hormones and inhibitors of this enzyme represent a new pharmacological treatment for several androgen dependent diseases. We developed a radiosubstrate in vitro incubation method for the determination of 5α-reductase type 1 activity using rat liver microsomes as an enzyme source. With this method we have studied the inhibiting activity of novel (5’S)-17ß-(4,5-dihydrooxazol-5-yl)androst-5-en-3-one compounds containing various derivatized phenyl substituents coupled to the exo-heterocyclic moiety. Tests revealed moderate inhibitory actions compared to finasteride, nevertheless, results provide interesting structure-activity relationship data.
Keywords5α-reductase inhibitors exo-heterocyclic steroids rat liver finasteride
Unable to display preview. Download preview PDF.
- 11.Li, X., Singh, S. M., Labrie, F. (1995) Synthesis and in vitro activity of 17ß-(N-alkyl/arylformamido)-and 17ßbeta-[(N-alkyl/aryl)alkyl/arylamido]-4-methyl-4-aza-3-oxo-5α-androstan-3-ones as inhibitors of human 5α-reductases and antagonists of the androgen receptor. J. Med Chem. 38, 1158–1173.CrossRefGoogle Scholar
- 20.Salem, O. I., Frotscher, M., Scherer, C., Neugebauer, A., Biemel, K., Streiber, M., Maas, R., Hartmann R. W. (2006) Novel 5alpha-reductase inhibitors: synthesis, structure-activity studies, and pharmacokinetic profile of phenoxybenzoylphenyl acetic acids. J. Med. Chem. 49, 748–759.CrossRefGoogle Scholar
- 22.Sun, Z. Y., Xie, H., Tu Z. H. (1999) Effect of Finasteride and Epristeride on steroid 5α-reductase kinetics - a comparative in vitro study. Ind. J. Pharmacol. 31, 120–123.Google Scholar
- 23.Sun, Z. Y., Zheng, W. J., Feng, J., Tu Z. H. (1998) A convenient and rapid method to study enzymatic kinetics of steroid 5α-reductase inhibitors. Ind. J. Pharmacol. 30, 257–282.Google Scholar
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.