@article{ref1,
title="Studies of the time-dependent inactivation of aromatase by 4beta,5beta-epoxy-6-one and 5beta,6beta-epoxy-4-one steroids under various conditions",
journal="Biological and pharmaceutical bulletin",
year="1999",
author="Numazawa, M. and Yamada, K.",
volume="22",
number="11",
pages="1207-1211",
abstract="The time-dependent inactivation of aromatase by epoxy analogs of the good aromatase inhibitors, androst-4-ene-6,17-dione (3) and androst-5-ene-4,17-dione (7), 4beta,5beta-epoxy and 5beta,6beta-epoxy compounds 10 and 13 and their 19-oxo derivatives 11 and 14, was examined in either the presence or absence of NADPH. The 4beta,5beta-epoxy-19-oxo steroid 11 along with the 19-methyl-5beta,6beta-epoxide 13 inactivated human placental aromatase in a mechanism-based manner, in the presence of NADPH, with rate constants for inactivation (k(inact)) of 0.133 min(-1) for steroid 11 and 0.100 min(-1) for steroid 13, whereas the two other steroids, 10 and 14, did not. On the other hand, none of four epoxides studied caused time-dependent inactivation of aromatase in an affinity-labeling manner in the absence of NADPH. These results are the first report showing that inhibitors 11 and 13 are suicide substrates having an epoxyketone structural feature.<p /><p>Language: en</p>",
language="en",
issn="0918-6158",
doi="10.1248/bpb.22.1207",
url="http://dx.doi.org/10.1248/bpb.22.1207"
}