Electrochemical Oxidation of Tamoxifen Revisited (original) (raw)
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Electrochemical behaviour and validated determination of the anitcancer drug Tamoxifen
2012
The electrooxidative behaviour of tamoxifen (Tam) and 4-hydroxytamoxifen (TamOH) was investigated by cyclic (CV), differential-pulse adsorptive anodic stripping (DPAdAS) and square-wave adsorptive anodic stripping (SWAdAS) voltammetric techniques. The anodic oxidation peak of Tamoxifen was attributed to the cyclization reaction to form the corresponding phenanthrene derivative and the mechanism of oxidation was postulated on the basis of controlled potential electrolysis and isolation of the oxidative product. Oxidative stripping analysis was successfully applied to the determination of tamoxifen in a bulk pharmaceutical formulation, and sensitivity in human urine and serum was validated. The achieved limits of detection (LOD) of bulk tamoxifen were 1.8 × 10 -6 mol L -1 and 2.4 × 10 -6 mol L -1 for DPAdAS and SWAdAS, respectively. The LOD values for tamoxifen in human urine and serum sample analysis were 4.75 × 10 -7 mol L -1 and 2.63 × 10 -7 mol L -1 and 1.98 × 10 -7 mol L -1 and 3...
ACS chemical biology, 2015
Tamoxifen is not only considered a very potent chemotherapeutic adjuvant for estrogen receptor positive breast cancers, but also a very good chemo-preventive drug. Recently there has been a rising amount of evidence for a non-genomic cytotoxicity of tamoxifen, even in estrogen receptor negative cells, which has greatly confounded researchers. Clinically the side-effects of tamoxifen can be very serious, ranging from liver steatosis to cirrhosis, tumorigenesis or onset of porphyrias. Herein, we deciphered the non-genomic, mitochondrial cytotoxicity of tamoxifen in estrogen receptor positive MCF7 versus triple-negative MDA-MB-231 cells, employing the mitochondrial complex III quinoloxidising-centre inhibitor myxothiazol. We showed a role for hydroxyl-radical-mediated lipid peroxidation, catalyzed by iron, stemming from the redox interactions of tamoxifen quinoid metabolites with complex III, resulting in Fenton-capable reduced quinones. The role of tamoxifen semiquinone species in mit...
ChemMedChem, 2015
Ferrociphenols have been found to have high antiproliferative activity against estrogen-independent breast cancer cells. The rat and human liver microsome-mediated metabolism of three compounds of the ferrocifen (FC) family, 1,1-bis(4-hydroxyphenyl)-2-ferrocenyl-but-1-ene (FC1), 1-(4-hydroxyphenyl)-1-(phenyl)-2-ferrocenyl-but-1-ene (FC2), and 1-[4-(3-dimethylaminopropoxy)phenyl]-1-(4-hydroxyphenyl)-2-ferrocenyl-but-1-ene (FC3), was studied. Three main metabolite classes were identified: quinone methides (QMs) deriving from two-electron oxidation of FCs, cyclic indene products (CPs) deriving from acid-catalyzed cyclization of QMs, and allylic alcohols (AAs) deriving from hydroxylation of FCs. These metabolites are generated by cytochromes P450 (P450s), as shown by experiments with either N-benzylimidazole as a P450 inhibitor or recombinant human P450s. Such P450-dependent oxidation of the phenol function and hydroxylation of the allylic CH2 group of FCs leads to the formation of QM a...