Synthesis and biological evaluation of novel unsaturated carboxysteroids as human 5α-reductase inhibitors: a legitimate approach

Eur J Med Chem. 2012 Aug:54:728-39. doi: 10.1016/j.ejmech.2012.06.026. Epub 2012 Jun 21.

Abstract

In the present study, novel steroidal 17a-substituted 3-cyano-17a-aza-D-homo-3,5-androstadien-17-ones (12-19) and 17a-substituted 17-oxo-17a-aza-D-homo-3,5-androstadien-3-oic acids (20-26) were synthesized from dehydroepiandrosterone acetate (6) along with 17-oxo-19-nor-3,5-androstadien-3-oic acid (30) through a multistep synthesis. Compounds were evaluated for their in vitro 5α-reductase inhibitory activity by measuring the conversion of [(3)H] androstenedione in human embryonic kidney (HEK) cells. In vivo 5α-reductase inhibitory activity was also determined using rat prostate weighing method. Compounds 21-23 and 25 showed potent inhibition of 5α-reductase II enzyme with IC(50) values of 54.1 ± 9.5, 22.1 ± 2.4, 72.8 ± 2.3 and 26.5 ± 4.4 nM respectively as compared to Finasteride (30.3 nM) along with a significant (p < 0.05) reduction in rat prostate weight.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-alpha Reductase Inhibitors / chemical synthesis*
  • 5-alpha Reductase Inhibitors / chemistry
  • 5-alpha Reductase Inhibitors / pharmacology*
  • Androstenedione / chemical synthesis*
  • Androstenedione / chemistry
  • Androstenedione / pharmacology*
  • Animals
  • Chemistry Techniques, Synthetic
  • Cholestenone 5 alpha-Reductase / antagonists & inhibitors*
  • HEK293 Cells
  • Humans
  • Inhibitory Concentration 50
  • Isoenzymes / antagonists & inhibitors
  • Male
  • Organ Size / drug effects
  • Prostate / anatomy & histology
  • Prostate / drug effects
  • Rats
  • Rats, Wistar

Substances

  • 5-alpha Reductase Inhibitors
  • Isoenzymes
  • Androstenedione
  • Cholestenone 5 alpha-Reductase