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 μM for 1 and 2 respectively on MDA-MB-231 and around 1 μM 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 1 and 99mTcO4− was used for the synthesis of 1-(p-(tricarbonylcyclopentadienyl-[99mTc]-technetium carboxy-amino-phenyl)-1,2-di(p-hydroxyphenyl)-but-1-ene, 3. 99mTc-3 was obtained in 70–75% yield. The in vivo biodistribution of purified 99mTc-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 17β-estradiol while that of most organs devoided of estrogen receptors remained unchanged.

Ferrocenyl, cymantrenyl triaryl butene derivatives were synthesized. Both compounds exhibit an antiproliferative effect against breast cancer cells. 99mTc analog was prepared from ferrocenyl derivative by using double metal exchange reaction. In vivo biodistribution of the Tc compound was studied in rats.Figure optionsDownload as PowerPoint slideHighlights
► Ferrocenyl, cymantrenyl and cytechtrenyl butene derivatives were synthesized.
► Ferrocenyl and cymantrenyl compounds exhibit an antiproliferative effect.
► 99mTc compound was prepared from its ferrocenyl analog by using double metal exchange reaction.
► Biodistribution of the Tc compound was studied in rats.