Testosterone 5 alpha-reductase inhibitors, menaquinone 7 produced by a Bacillus and phenazine methosulfate.
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.
Kim
Y U
YU
College of Pharmacy, Seoul National University, Korea.
Kim
C H
CH
Son
H K
HK
Song
H K
HK
Han
J
J
Lee
S S
SS
Lee
S K
SK
D058891:5-alpha Reductase Inhibitors; D000818:Animals; D001407:Bacillus / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008773:Methylphenazonium Methosulfate / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014812:Vitamin K / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D024482:Vitamin K 2 / Q000031:analogs & derivatives*
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D024482:Vitamin K 2; D014812:Vitamin K; D008773:Methylphenazonium Methosulfate; C062629:menaquinone 7