Testosterone 5α-Reductase Inhibitors, Menaquinone 7 Produced by a Bacillus and Phenazine Methosulfate

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 5α-reductase inhibitor with an IC₅₀ value of 4.0×10^-5 M from the cultured broth. Phylloquinone was as active as the purified microbial metabolite with an IC₅₀ value of 6.6×10^-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 5α-reductase were tested, and the IC₅₀ values were 3.1×10^-6 M, 4.9×10^-8 M, 8.9×10^-5 M, respectively. A product of the 5α-reductase enzyme reaction and an electron and proton carrier, NADP⁺, inhibited the 5α-reduction by rat prostate testerone 5α-reductase with an IC₅₀ value of 9.2×10^-5 M. However, the inhibition effect of a proton carrier, carbonylcyanide-m-chlorophenylhydrazone, for rat prostate testosterone 5α-reductase was substantially inactive.