title: Inhibition of human topoisomerase I and II and anti-proliferative effects on MCF-7 cells by new titanocene complexes.
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, C5H5) 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.
authors.affiliation: Department of Pharmacy, Health and Nutrition Sciences, University of Calabria, Arcavacata di Rende, Cosenza, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Chimento
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Fisciano (SA), Italy. Electronic address: saturnino@unisa.it.
authors.forename: Carmela
authors.initials: C
authors.lastname: Saturnino
authors.affiliation: Department of Pharmacy, Health and Nutrition Sciences, University of Calabria, Arcavacata di Rende, Cosenza, Italy. Electronic address: domenico.iacopetta@unical.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Iacopetta
authors.affiliation: Department of Pharmacy, Health and Nutrition Sciences, University of Calabria, Arcavacata di Rende, Cosenza, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Mazzotta
authors.affiliation: Department of Pharmacy, Health and Nutrition Sciences, University of Calabria, Arcavacata di Rende, Cosenza, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Caruso
authors.affiliation: Department of Chemistry, University of Messina and Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici (CIRCMSB), Vill. S. Agata, Messina, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Plutino
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Fisciano (SA), Italy.
authors.forename: Annaluisa
authors.initials: A
authors.lastname: Mariconda
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Fisciano (SA), Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Ramunno
authors.affiliation: Department of Pharmacy, Health and Nutrition Sciences, University of Calabria, Arcavacata di Rende, Cosenza, Italy. Electronic address: s.sinicropi@unical.it.
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: Sinicropi
authors.affiliation: Department of Pharmacy, Health and Nutrition Sciences, University of Calabria, Arcavacata di Rende, Cosenza, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pezzi
authors.affiliation: Department of Chemistry and Biology, University of Salerno, Fisciano (SA), Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Longo
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008856:Microscopy, Fluorescence; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D009942:Organometallic Compounds; C518838:Titanocene Y; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C406884:titanocene; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II
keywords: Cell death; MCF-7 cells; Titanocene complexes; Topoisomerase I; Topoisomerase II; cis-Platin