Synthesis and antiproliferative evaluation of ferrocenyl and cymantrenyl triaryl butene on breast cancer cells. Biodistribution study of the corresponding technetium-99m tamoxifen conjugate

1-(p-(ferrocenylcarbonylamino-phenyl)-1,2-di(p-hydroxyphenyl)-but-1-ene, 1, and 1-(p-(cymantrenylcarbonylamino-phenyl)-1,2-di(p-hydroxyphenyl)-but-1-ene, 2, were synthesized. Both compounds exhibit a significant antiproliferative effect against hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cells (IC50 = 4.5 and 9.4 mu M for 1 and 2 respectively on MDA-MB-231 and around 1 mu M for 1 and 2 on MCF-7 cells). Interestingly, 2 is the first cymantrenyl complex in this triaryl butene series to show such a high cytotoxic effect. A metal exchange reaction between I and (TcO4-)-Tc-99m was used for the synthesis of 1-(p-(tricarbonylcyclopentadienyl-[Tc-99m]-technetium carboxy-amino-phenyl)-1,2-di(p-hydroxyphenyl)-but-1-ene, 3. Tc-99m-3 was obtained in 70-75% yield. The in vivo biodistribution of purified Tc-99m-3 was undertaken on mature female Wistar rats. The uptake by organs follows the order: liver > lung > kidney > heart > spleen > ovaries > bone > muscle > uterus. The ovaries/muscle ratio was 3.89 while that of uterus/muscle ratio was 0.99. Uptake in ovaries was abolished by co-administration of 17 beta-estradiol while that of most organs devoided of estrogen receptors remained unchanged. (C) 2012 Elsevier B.V. All rights reserved.