Synthesis and in vitro biological activity of new non-steroidal platinum (II) complexes designed for the treatment of breast cancer

He, Yuehua (1995) Synthesis and in vitro biological activity of new non-steroidal platinum (II) complexes designed for the treatment of breast cancer. Masters thesis, Memorial University of Newfoundland.

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Abstract

Breast cancer is the leading form of cancer among women in North America. The development of resistance to endocrine therapy as well as chemotherapy is presently the major obstacle to successful treatment of advanced breast cancer. Therefore, more potent and selective chemotherapeutic agents should be designed. An attractive solution to this problem is to combine both endocrine therapy and chemotherapy in a single agent. It may result in a more powerful approach to advanced breast cancer treatment. -- In order to achieve this goal, a series of new triphenylethylene platinum (II) complexes 39a-d, 40a-c and 41 have been designed and synthesized. The commercially available benzyl, 4-hydroxyphenyl ketone was efficiently transformed in eight steps into the platinum (II) complexes 39a-d with an overall yield of around 30%. In a similar sequence of reactions, the complexes 40a-c and 41 were also synthesized, the overall yield exceeded 40%. All new compounds were fully characterized by their infrared and ¹H, ¹³C nuclear magnetic resonance and mass spectra. The final compounds 39a-d, 40a-c and 41 also passed element analysis. -- The biological activity of the complexes 39a-d, 40a-c and 41 were evaluated in vitro on both ER⁺ and ER⁻ breast cancer cell lines: MCF-7 and MDA-MD-231. The complexes 40b-c showed promising antitumor activity. Their IC₅₀ is up to 28 fold lower than tamoxifen on MDA-MD-231, and 3 fold lower on MCF-7. However, there was no evidence of selective antitumor activity on ER⁺ breast cancer cell in vitro.

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