Inhibition of human topoisomerase I and II and anti-proliferative effects on MCF-7 cells by new titanocene complexes

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• 作者：Adele Chimento^a ; ^&dagger ; ; Carmela Saturnino^b ; ^&dagger ; ; ^{saturnino@unisa.it" class="auth_mail" title="E-mail the corresponding author} ; Domenico Iacopetta^a ; ^{domenico.iacopetta@unical.it" class="auth_mail" title="E-mail the corresponding author} ; Rosaria Mazzotta^a ; Anna Caruso^a ; Maria Rosaria Plutino^c ; Annaluisa Mariconda^b ; Anna Ramunno^b ; Maria Stefania Sinicropi^a ; ^{s.sinicropi@unical.it" class="auth_mail" title="E-mail the corresponding author} ; Vincenzo Pezzi^a ; ^&Dagger ; ; Pasquale Longo^d ; ^&Dagger ;
• 关键词：DMSO ; dimethyl sulfoxide ; THF ; tetrahydrofuran ; ADP ; adenosine diphosphate ; ATP ; adenosine triphosphate ; DAPI ; 4&prime ; 6-diamidino-2-phenylindole ; DMEM/F-12 ; Dulbecco&rsquo ; 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
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2015
• 出版时间：15 November 2015
• 年：2015
• 卷：23
• 期：22
• 页码：7302-7312
• 全文大小：2010 K

文摘

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.