Testosterone 5 alpha-reductase inhibitors, menaquinone 7 produced by a Bacillus and phenazine methosulfate

Biol Pharm Bull. 1999 Dec;22(12):1396-9. doi: 10.1248/bpb.22.1396.

Abstract

Menaquinone 7 (MW: 649, C46H64O2), a natural electron acceptor for steroid ring A dehydrogenations, produced by Bacillus sp. SNU-299, was isolated as a rat prostate testosterone 5 alpha-reductase inhibitor with an IC50 value of 4.0 x 10(-5) M from the cultured broth. Phylloquinone was as active as the purified microbial metabolite with an IC50 value of 6.6 x 10(-4) M. On the basis of this evidence, the inhibitory activities of electron carriers, menadione, phenazine methosulfate, and 2,6-dichlorophenolindophenol, for rat prostate testosterone 5 alpha-reductase were tested, and the IC50 values were 3.1 x 10(-6) M, 4.9 x 10(-8) M, 8.9 x 10(-5) M, respectively. A product of the 5 alpha-reductase enzyme reaction and an electron and proton carrier, NADP+, inhibited the 5 alpha-reduction by rat prostate testosterone 5 alpha-reductase with an IC50 value of 9.2 x 10(-5) M. However, the inhibition effect of a proton carrier, carbonylcyanide-m-chlorophenylhydrazone, for rat prostate testosterone 5 alpha-reductase was substantially inactive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-alpha Reductase Inhibitors*
  • Animals
  • Bacillus / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Male
  • Methylphenazonium Methosulfate / pharmacology*
  • Prostate / drug effects*
  • Prostate / enzymology
  • Rats
  • Rats, Sprague-Dawley
  • Vitamin K / analogs & derivatives*
  • Vitamin K / isolation & purification
  • Vitamin K / pharmacology
  • Vitamin K 2* / analogs & derivatives*

Substances

  • 5-alpha Reductase Inhibitors
  • Enzyme Inhibitors
  • Vitamin K 2
  • Vitamin K
  • Methylphenazonium Methosulfate
  • menaquinone 7