Organometallic cyclic polyphenols derived from 1,2-(α-keto tri or tetra methylene) ferrocene show strong antiproliferative activity on hormone-independent breast cancer cells

We have previously shown that achiral ferrocenyl diphenol butene derivatives are strong antitumor agents against both hormone-dependent and -independent breast cancer cell lines We report now examples of a new series of two planar chiral diphenol derivatives, namely 1,2-[1-[1,1-bis(4-hydroxyphenyl)methylidene]trimethylene] ferrocene (4), and 1,2-[1-[1,1-bis(4-hydroxyphenyl)methylidene]tetramethylene]ferrocene (5) They were prepared under racemic form from a McMurry coupling reaction with 30% and 16% yields, respectively Compound 5 gave crystals suitable for X-ray structural analysis Compounds 4 and 5 were tested for ER alpha and ER beta affinity, lipophilicity, and proliferative/antiproliferative effects against the hormone-dependent breast cancer cell line MCF-7, and the hormone-independent breast cancer cell line MDA-MB-231 Both compounds exhibit better affinity for ER beta (16 4 +/- 0 1 and 7 0 +/- 0 4, respectively) than for ER alpha (6 4 +/- 0 2, and 6 6 0 2) The test on hormone-independent breast cancer cell line M DA-MB-231 showed that 4 with a 5-membered ring gives an IC50 value of 2 7 mu M while with 5 in which the ring has 6 carbons, the value is reduced to IC50 = 1 23 mu M