Tamoxifen, anticancer activity

As mentioned in the introduction, metallocene-type complexes based on the early transition metals were evaluated as anticancer compounds shortly after the discovery of cisplatin. While the biological activity of each of the metallocene dihalides is unique, titanocene dichloride 7 has been the subject of a number of studies and even entered clinical evaluation, although evaluation was discontinued (not due to its anti-proliferative properties), principally due to formulation problems, despite showing superior activity to certain cancers than other established drugs. This class of compound continues to be modified and studied for anticancer activity, for example, the titanocene-type derivative of tamoxifen 1, described above, and other developments described below. 

Structurally related to the phytoalexins resveratrol and pterostilbene. Resveratrol is found in the skins of red grapes, other fruits and red wine, while pterostilbene is found in grapes and blueberries. Resveratrol possesses oestrogenic activity and has been investigated for anticancer activity. These compounds also have structural similarities with the anticancer drug tamoxifen (Figure 13.22). 

Custodio JB, Almeida LM, Madeira VM (1993) The active metabolite hydroxytamoxifen of the anticancer drug tamoxifen induces structural changes in membranes. Biochim Biophys Acta 1153(2) 308-314... 

Rhenium tricarbonyl complexes containing substituted cyclopentadi-enyl and bis diphenylphosphine ligands also were investigated as anticancer agents. The antiproliferative effects on breast cancer of complex A shown in Fig. 23 were examined relative to the known active metabolite, 4-hydroxy tamoxifen, and found to have a similar effect [107]. The cytotoxicity of five rhenium tricarbonyl bis-diphenylphosphine complexes B shown in Fig. 23 was examined for 18 different human cancer cell lines. The tests showed that all the complexes were active against specific tumor cell lines, especially a line of breast and uterine cancer [108]. 

This chapter reviews the bioanalytical developments by mass spectrometry in the field of targeted anticancer therapy, across the growing family of recent FDA-approved oral TKIs as well as tamoxifen and its active metabolites. The text also provides an introduction to existing pharmacokinetics-pharmacodynamics knowledge in the field of targeted anticancer therapy. 

Coradini D, Biffi A, Cappelletti V, Fronzo GD (1994) Activity of tamoxifen and new antiestrogens on estrogen-receptor positive and negative breast-cancer cells. Anticancer Res 14 1059-1064... 

Foster AB, McCague R, Seago A, Leclercq G, Stoessel S, Roy F (1986) Modification of the basic side chain in tamoxifen effects on microsomal metabolism and in vitro biological activity. Anticancer Drug Des 1 245-257... 

---