Biological evaluation of twenty-eight ferrocenyl tetrasubstituted olefins: Cancer cell growth inhibition, ROS production and hemolytic activity

• Published in: European journal of medicinal chemistry 2011-09, Vol.46 (9), p.3778-3787
• Main Authors: de Oliveira, Alane Cabral, Hillard, Elizabeth A., Pigeon, Pascal, Rocha, Danilo Damasceno, Rodrigues, Felipe A.R., Montenegro, Raquel C., Costa-Lotufo, Letícia V., Goulart, Marilia O.F., Jaouen, Gérard
• Format: Article
• Language: English
• Subjects: Alkenes - chemistry; Alkenes - pharmacology; Antineoplastic agents; Biological and medical sciences; Bioorganometallics; Cancer; Cancer cell line; Cell Division - drug effects; Cell Line, Tumor; Chemical Sciences; Coordination chemistry; Cytotoxicity; Drug Screening Assays, Antitumor; Ferrocene; Ferrocifen; Ferrous Compounds - chemistry; General aspects; Hemolysis; Hemolysis - drug effects; Humans; Inhibitory Concentration 50; Life Sciences; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medical sciences; Medicinal Chemistry; Metallocenes; Neoplasms - metabolism; Neoplasms - pathology; Pharmacology. Drug treatments; Reactive Oxygen Species - metabolism; Spectrophotometry, Infrared; Structure–activity relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2011.05.043

The antiproliferative effects of twenty-eight tetrasubstituted olefins bearing a ferrocenyl group, including six never-reported compounds, were evaluated against SF-295 (human glioblastoma), HCT-8 (human colon cancer), MDA-MB-435 (human melanoma) and HL-60 (human promyelocytic leukemia) using the MTT test. IC 50 values were determined for twenty-three active compounds and of these, ten compounds had IC 50 values lower than 2 μM on one or more cell lines. Of all the compounds, only two produced significant amounts of ROS on HL-60 cells, and ROS production and growth inhibition could not be correlated. The ten most antiproliferative compounds were tested for their hemolytic activity on mouse erythrocytes. Five compounds showing high antiproliferative activity and low hemolytic activity were thus identified for further study. [Display omitted] ► Ferrocene compounds show low micromolar activity against cancer cells. ► Aminated ether substituents contribute to activity, but also to hemolysis. ► ROS production in HL-60 does not correlate with activity. ► MDA-MB-435 melanoma cells are resistant to most ferrocenyl compounds.