title: Ferrocenes as potential chemotherapeutic drugs: synthesis, cytotoxic activity, reactive oxygen species production and micronucleus assay.
abstract: Three new ferrocene complexes were synthesized with 4-(1H-pyrrol-1-yl)phenol group appended to one of the Cp ring. These are: 1,1'-4-(1H-pyrrol-1-yl)phenyl ferrocenedicarboxylate, ('Fc-(CO2-Ph-4-Py)2'), 1,4-(1H-pyrrol-1-yl)phenyl, 1'-carboxyl ferrocenecarboxylate ('Fc-(CO2-Ph-4-Py)CO2H') and 4-(1H-pyrrol-1-yl)phenyl ferroceneacetylate ('Fc-CH2CO2-Ph-4-Py'). The new species were characterized by standard analytical methods. Cyclic voltammetry experiments showed that Fc-CH2CO2-Ph-4-Py has redox potential very similar to the Fc/Fc(+) redox couple whereas Fc-(CO2-Ph-4-Py)2 and Fc-(CO2-Ph-4-Py)CO2H have redox potentials of over 400 mV higher than Fc/Fc(+) redox couple. The in vitro studies on Fc-(CO2-Ph-4-Py)2 and Fc-(CO2-Ph-4-Py)CO2H revealed that these two compounds have moderate anti-proliferative activity on MCF-7 breast cancer cell line. In contrast Fc-CH2CO2-Ph-4-Py which displayed low anti-proliferative activity. In the HT-29 colon cancer cell line, the new species showed low anti-proliferative activity. Cytokinesis-block micronucleus assay (CBMN) was performed on these ferrocenes and it was determined they induce micronucleus formation on binucleated cells and moderate genotoxic effects on the MCF-7 breast cancer cell line. There is a correlation between the IC50 values of the ferrocenes and the amount of micronucleus formation activity on binucleated cells and the reactive oxygen species (ROS) production on MCF-7 cell line.
authors.affiliation: Department of Chemistry, University of Puerto Rico, PO Box 9019, Mayagüez, PR 00681, United States.
authors.forename: Wanda I
authors.initials: WI
authors.lastname: Pérez
authors.affiliation: Department of Biotechnology, University of Puerto Rico, PO Box 9019, Mayagüez, PR 00681, United States.
authors.forename: Yarelys
authors.initials: Y
authors.lastname: Soto
authors.affiliation: Department of Pharmacology, Toxicology and Physiology, Ponce School of Medicine and Health Sciences, Ponce, PR 00732-7004, United States.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ortíz
authors.affiliation: Department of Pharmacology, Toxicology and Physiology, Ponce School of Medicine and Health Sciences, Ponce, PR 00732-7004, United States.
authors.forename: Jaime
authors.initials: J
authors.lastname: Matta
authors.affiliation: Department of Chemistry, University of Puerto Rico, PO Box 9019, Mayagüez, PR 00681, United States. Electronic address: enrique.melendez@upr.edu.
authors.forename: Enrique
authors.initials: E
authors.lastname: Meléndez
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D000075163:Metallocenes; D015162:Micronucleus Tests; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D005296:Ferrous Compounds; D000075163:Metallocenes; D017382:Reactive Oxygen Species; C004998:ferrocene
keywords: Anti-proliferative; Cytokinesis-block micronucleus assay; Ferrocene; HT-29; MCF-10A; MCF-7