Inhibition of human topoisomerase I and II and anti-proliferative effects on MCF-7 cells by new titanocene complexes. Issue 22 (15th November 2015)

• Record Type: Journal Article
• Authors: Chimento, Adele; Saturnino, Carmela; Iacopetta, Domenico; Mazzotta, Rosaria; Caruso, Anna; Plutino, Maria Rosaria; Mariconda, Annaluisa; Ramunno, Anna; Sinicropi, Maria Stefania; Pezzi, Vincenzo; Longo, Pasquale
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 22(2015)
• Page Start: 7302
• Page End: 7312
• Publication Date: 2015-11-15
• Subjects: DMSO dimethyl sulfoxide -- THF tetrahydrofuran -- ADP adenosine diphosphate -- ATP adenosine triphosphate -- DAPI 4′, 6-diamidino-2-phenylindole -- DMEM/F-12 Dulbecco's modified eagle medium: nutrient mixture F-12 -- DNA deoxyribonucleic acid -- EDTA ethylenediaminetetraacetic acid -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- NAD nicotinamide adenine dinucleotide -- Parp-1 poly(ADP-ribose)polymerase 1 -- RNA ribonucleic acid; Titanocene complexes -- cis-Platin -- MCF-7 cells -- Topoisomerase I -- Topoisomerase II -- Cell death; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.10.030
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: The antitumor activity shown by many platinum complexes has produced a strong interest in research of new organometallic compounds having anticancer action. Among the many metal compounds synthesized and tested, those based on titanium have received considerable attention because of their cytotoxic activity against solid tumors. Particularly, new titanocene compounds containing aromatic groups linked to the Cp (cyclopentadienyl ring, C5 H5 ) have been synthetized, such as the titanocene Y (bis-[( p -methoxybenzyl)cyclopentadienyl]titanium dichloride) that displayed promising medium–high cytotoxic activity on breast cancer cell lines. Other titanocene complexes recently synthesized, obtained by replacing the substituent methoxy-aryl of cyclopentadienes of titanocene Y with ethenyl-methoxide or ethenyl-phenoxide, showed increased cytotoxic activity on breast cancer cell lines being more stable compounds. In this paper, we report that new titanocene complexes holding lipophilic groups, for instance a methyl group on benzyl carbon, exhibit improved antiproliferative effect on breast cancer cell line MCF-7. Similar results have been obtained introducing a 5-methoxy naphthyl group to further stabilize the titanocene complexes. These inhibitory effects on breast cancer cells have been ascribed to human topoisomerase I and II inhibition as demonstrated by specific enzymatic assays.