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

Abstract 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 (IC 50 = 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 99m TcO 4 − was used for the synthesis of 1-(p-(tricarbonylcyclopentadienyl-[ 99m Tc]-technetium carboxy-amino-phenyl)-1,2-di(p-hydroxyphenyl)-but-1-ene, 3 . 99m Tc- 3 was obtained in 70–75% yield. The in vivo biodistribution of purified 99m Tc- 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.