Well, I found where this data is being drawn from. It does exert anti-aromatase activity, but in this case at the expense of, as a competitive inhibitor of, androstenedione...which as we all know by know is a few steps away in testosterone's production. This gets back to why one would do this unless its for a short period in a hyperestrogenic state, further, as stated previously it will be at the expense of testosterone, as anti-androgen as well if used for any notable period of time. This is from 1. 1987 2. Hardly, a strong credentialed, peer-referenced, stringently reviewed journal 3. Is with rabbits regarding placental aromatase. But taking it for a noteworthy place to start, it is that. There is another Japanese journal publication that uses the 1987 data and elaborates further on the rabbit data with the discussion on the activity of various groups in the molecule...which is a bit more conflicting then stated above in the typical muscle magazine marketing sort of way. But for anyone interested here's the elusive data that's being somewhat distorted and extrapolated.
Endocrinology, Vol 121, 1010-1016, Copyright © 1987 by Endocrine Society
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Stereochemistry of the functional group determines the mechanism of aromatase inhibition by 6-bromoandrostenedione
Y Osawa, Y Osawa and MJ Coon
A selective inhibitor of aromatase (estrogen synthetase) would be a useful pharmacological tool with potential therapeutic application. We have found that 6 alpha-bromoandrostenedione (6 alpha-BrA) is a competitive inhibitor of human placental aromatase with respect to androstenedione, with an apparent Ki of 3.4 nM, while 6 beta-BrA is a mechanism-based irreversible inhibitor with an apparent Ki of 0.8 microM and a kinact of 0.025 min-1. Aromatase activity was measured by tritium release into water from the 1 beta position of [1(-3)H,4(- 14)C]androstenedione in reaction mixtures containing NADPH and the aromatase. Time-dependent inhibition was assessed by preincubation of inhibitors with either the 900 X g placental pellet or placental microsomes in the presence of NADPH. Aliquots were taken at intervals, diluted, and assayed for aromatase activity with androstenedione and additional NADPH. The time-dependent inhibition by 6 beta-BrA was dependent on the concentration of this compound and the presence of NADPH, while the addition of excess substrate in the preincubation mixture hindered the inactivation. Both epimers were ineffective in inhibiting rabbit liver microsomal drug-metabolizing activities in a competitive or time-dependent manner. This indicates a high selectivity of 6-BrA inhibition among P-450 cytochromes. These and other 6- substituted androgens may be useful probes into the nature of the active site and mechanism of action of aromatase.
Biol Pharm Bull. 2004 Nov;27(11):1878-82. Related Articles, Links
Synthesis and biochemical properties of 6-bromoandrostenedione derivatives with a 2,2-dimethyl or 2-methyl group as aromatase inhibitors.
Numazawa M, Handa W, Yamada K.
Tohoku Pharmaceutical University, Sendai, Japan.
[email protected]
To gain insight into the mechanism for irreversible inactivation of aromatase by 6beta-bromoandrostenedione (1), one of the earliest discovered suicide substrates, in relation to the catalytic function of the enzyme, the 2,2-dimethyl derivative of compound 1, steroid 4, and its 6alpha-isomer 5, as well as 2-methyl-1,4-diene steroid 8 and its 6alpha-bromide 10, were synthesized. All of the steroids inhibited aromatase activity in human placental microsomes with apparent K(i)'s ranging between 10 and 81 nM. The 2,2-dimethyl-6beta- and 6alpha-bromo steroids 4 and 5 were extremely powerful inhibitors (K(i): 14 and 10 nM, respectively), but these two did not cause a time-dependent inactivation of aromatase in the presence of NADPH; in contrast, the 2-methyl-1,4-diene steroids 8 and 10 caused time-dependent inactivation with apparent k(inact) of 0.035 and 0.071 min(-1), respectively, in a suicide manner. These results indicate that the 2,2-dimethyl function of the 6beta-bromide 4 would prevent the inactivation of aromatase caused by inhibitor 1 in a suicide manner, probably through steric activity, whereas the 2-methyl group of steroid 8 did not significantly affect the suicidal inactivation by the parent 1,4-diene steroid, a typical suicide substrate.
I take it at break fast, post w/o and before bed.