title: Functionalized ferrocenes: The role of the para substituent on the phenoxy pendant group.
abstract: Six ferrocenecarboxylates with phenyl, 4-(1H-pyrrol-1-yl)phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl as pendant groups were synthesized and fully characterized by spectroscopic, electrochemical and X-ray diffraction methods. The anti-proliferative activity of these complexes were investigated in hormone dependent MCF-7 breast cancer and MCF-10A normal breast cell lines, to determine the role of the para substituent on the phenoxy pendant group. The 4-fluorophenyl ferrocenecarboxylate is inactive in both cell lines while 4-(1H-pyrrol-1-yl)phenyl ferrocenecarboxylate is highly cytotoxic in both cell lines. 4-chlorophenyl and 4-bromophenyl ferrocenecarboxylates have moderate to good anti-proliferative activity in MCF-7 and low anti-proliferative activity on normal breast cell line, MCF-10A whereas the 4-iodophenyl analog is highly toxic on normal breast cell line. The phenyl ferrocenecarboxylate has proliferative effects on MCF-7 and is inactive in MCF-10A. Docking studies between the complexes and the alpha-estrogen receptor (ERα) were performed to search for key interactions which may explain the anti-proliferative activity of 4-bromophenyl ferrocenecarboxylate. Docking studies suggest the anti-proliferative activity of these ferrocenecarboxylates is attributed to the cytotoxic effects of the ferrocene group and not to anti-estrogenic effects.
authors.affiliation: University of Puerto Rico, Department of Chemistry, PO Box 9019, Mayagüez 00681, Puerto Rico.
authors.forename: José L
authors.initials: JL
authors.lastname: Vera
authors.affiliation: University of Puerto Rico, Department of Chemistry, PO Box 9019, Mayagüez 00681, Puerto Rico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Rullán
authors.affiliation: University of Puerto Rico, Department of Chemistry, PO Box 9019, Mayagüez 00681, Puerto Rico.
authors.forename: Natasha
authors.initials: N
authors.lastname: Santos
authors.affiliation: University of Puerto Rico, Department of Chemistry, PO Box 9019, Mayagüez 00681, Puerto Rico.
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez
authors.affiliation: University of Puerto Rico, Department of Chemistry, PO Box 9019, Mayagüez 00681, Puerto Rico.
authors.forename: Joshua
authors.initials: J
authors.lastname: Rivera
authors.affiliation: University of Puerto Rico, Department of Chemistry, PO Box 9019, Mayagüez 00681, Puerto Rico.
authors.forename: Alberto
authors.initials: A
authors.lastname: Santana
authors.affiliation: University of California-San Diego, Department of Chemistry, Urey Hall 5128, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Briggs
authors.affiliation: University of California-San Diego, Department of Chemistry, Urey Hall 5128, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA.
authors.forename: Arnold L
authors.initials: AL
authors.lastname: Rheingold
authors.affiliation: Department of Pharmacology, Toxicology and Physiology, Ponce School of Medicine and Health Sciences, Ponce 00732-7004, Puerto Rico.
authors.forename: Jaime
authors.initials: J
authors.lastname: Matta
authors.affiliation: University of Puerto Rico, Department of Chemistry, PO Box 9019, Mayagüez 00681, Puerto Rico.
authors.forename: Enrique
authors.initials: E
authors.lastname: Meléndez
keywords: Anti-cancer; Docking; Estrogen receptor; Ferrocenecarboxylate; MCF-10A; MCF-7