Synthetic isoflavones and doping: A novel class of aromatase inhibitors?

Abstract

Anectodical information suggests that flavonoids may be widely used among athletes for their multiple biochemical and pharmacological effects. We have evaluated in vitro the effects of two synthetic isoflavones, methoxyisoflavone and ipriflavone, on the catalytic activity of human aromatase (CYP19), the enzyme catalyzing the conversion of androgens (ie, testosterone or androstenedione) to estrogens (ie, estradiol and estrone). The potential inhibitory effect was evaluated by measuring the rate of aromatization of testosterone, monitored by gas chromatography-mass spectrometry (GC-MS), both in the presence and in the absence of methoxyisoflavone or ipriflavone, comparing their effects with those of synthetic aromatase inhibitors (formestane, anastrozole, and aminoglutethimide) presently included in the list of prohibited substances and methods, and of natural flavonoids (chrysin, quercetin, and daidzein), that are known inhibitors of CYP19. The preliminary results of our in vitro study show that methoxyisoflavone and ipriflavone act as competitive inhibitors of aromatase, the degree of inhibition measured in vitro being of the same order of magnitude of that of the aromatase inhibitors commonly used in anti-estrogenic therapies. Our preliminary in vitro results indicate that, in principle, a sufficiently large intake of isoflavones could alter the kinetics of the dynamic equilibria between androgens and estrogens, suggesting their monitoring in doping control routine analysis.

Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds against Cancer

“…Firstly, the A and C rings of the flavonoids are structurally similar to the D and C rings of the aromatase substrate androstenedione, and secondly, the presence of oxo-group at the C4 position, which is essential for binding iron atoms of the heme group of aromatases [ 147 ]. Similar activity was also observed for apigenin [ 148 , 149 , 150 , 151 ]. In breast carcinoma cells, the antiproliferative effects of genistein were mediated by an intracellular metabolite, which inhibited cell cycle progression.…”

Inhibitory effect of chrysin on estrogen biosynthesis by suppression of enzyme aromatase (CYP19): A systematic review

“…The K i values of ipriflavone and methoxyisoflavone were 0.19 μM and 0.36 μM, respectively. Thus, two synthetic isoflavones were competitive aromatase inhibitors [5].…”

“…Phenolic compounds are classified into different groups such as flavonoids, phenolic alcohols, phenolic acids, stilbenes and lignans. The largest group of phenolic compounds with low molecular weight is flavonoids that are widely found in fruits and plants and are divided into six groups including flavanones, flavones, isoflavones, flavonols, flavanols as well as anthocyanins [5,6] and proanthocyanidins [7]. Secondary metabolites like flavonoids function as the first line of defense against oxygen radical production, ultraviolet rays and/or invasive organisms in plant species.…”

An investigation on the metabolic pathways of synthetic isoflavones by gas chromatography coupled to high accuracy mass spectrometry

“…Although the potential biological activity of the different metabolites has not been assessed yet, natural isoflavones, such as daidzein, are potent antioxidants and are also endowed with a significant antiestrogenic activity through inhibition of aromatase (CYP19) . For the above reasons, and also considering that methoxyisoflavone and ipriflavone have recently been shown by our group to inhibit the catalytic activity of CYP 19 in vitro , we believe that screening for their intake by targeting their urinary metabolites will be extremely helpful in routine doping control analysis, especially as far as the evaluation of the urinary steroid profile, i.e. the steroidal module of the Athlete Biological Passport, is concerned.…”