Tamoxifen cation

The tamoxifen cation (48), which can be thought of as the ultimate tamoxifen carcinogen, has been the subject of a detailed study. Its lifetime is 125 p,s if the amine is neutral and 22 p,s if it is protonated in either case it only reacts at the CH group. This makes it a relatively long-lived electrophile by carbocation standards, approaching the lifetime of tfiaryhnethyl cations. The steric and electronic factors involved in the... 

Allen MC,NewlandC,ValverdeMA, Hardy SP (1998) Inhibition ofligand-gated cation-selective channels by tamoxifen. Eur J Pharmacol 354(2—3) 261-269... 

The complexes with the shortest dimethyl amino side chains (n = 2, 3, or 4) retain the best affinity for the two forms of the estradiol receptor. On MCF7 hormone-dependent breast cancer cells, the anti-proliferative effect of these complexes at molarities of 1 xM is slightly stronger than that of OH-Tam for complexes where = 3 and 5 3b and 3d, and this effect is not completely suppressed by addition of estradiol. This seems to indicate that the observed anti-proliferative effect is the combination of an antihormonal effect linked to the tamoxifen skeleton and mediated by the estradiol receptor, and a cytotoxic effect induced by the presence of the ferrocenyl substituent. In fact, the cytotoxic properties of the ferricinium cation (Fc ), which is easily formed by oxidation in biological media, are well known.It should however be noted that ferrocene alone has no effect despite being able to enter cells without difficulty. 

Tamoxifen. The antiestrogenic drug, tamoxifen, is used in the treatment of advanced breast cancer, although it fi-equently causes steatosis in overweight women (Bruno et al. 2005). This cationic amphiphilic drug accumulates electro-phoretically in mitochondria, where it directly inhibits mitochondrial respiratiOTi and mitochondrial (3-oxidation, thus causing steatosis (Larosche et al. 2007). 

Tamoxifen. The antiestrogen, tamoxifen, is a cationic amphiphilic drug which is electrophoretically transported into the mitochondrial matrix where it reaches high concentrations that directly inhibit both mitochondrial p-oxidation and mitochondrial respiration, and also deplete mtDNA in mice, as mentioned above (Larosche et al. 2007). 

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