title: Improving the bioactivity of Zn(II)-curcumin based complexes.
abstract: New Zn(II)-curcumin based heteroleptic complexes (1-5) have been synthesized and fully characterized, with the aim to improve the bioactivity of the precursor derivative [(bpy-9)Zn(curc)Cl] (A), a potentially intercalating antitumor agent recently reported. Some structural changes have been made starting from the reference complex A, in order to introduce new functionalities, such as electrostatic and/or covalent interactions. In particular, keeping the same N,N chelating ligand, namely bpy-9, two completely different Zn(II) species have been obtained: a tetracoordinated Zn(II) cation with tetrafluoroborate as counterion (1) and a dimeric neutral complex in which the sulfate anion acts as a bridging group through two Zn(II) centres (2). Moreover, by changing the N,N chelating unit, [(L(n))Zn(curc)Cl] complexes (3-5), in which the Zn(II) ion shows the same pentacoordination seen in the precursor complex A, have been obtained. The antitumour activity of all new Zn(II) complexes was tested in vitro against the human neuroblastoma cell line SH-SY5Y in a biohybrid membrane system and the results indicate that all species exhibit strong cytotoxic activity. In particular the ionic tetrafluoroborate Zn(II) complex, 1, and the neutral phenanthroline based Zn(II) derivative, 4, show the strongest growth inhibition, being even more effective than the model complex A. Both complexes have a dose-dependent anti-proliferative effect on cells as demonstrated by the decrease of viability and the increase of Annexin V and PI-positive cells with the increase of their concentration. Cells treated with complexes 1 and 4 undergo apoptosis that involves the activation of JNK, caspase 3 and MMP changes. Finally, complex 1 is more effective in the induction of caspase-3 activation demonstrating its ability to trigger the execution-phase of cell apoptosis.
authors.affiliation: Centro di Eccellenza CEMIF.CAL-LASCAMM, CR-INSTM Unità della Calabria, Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, Via P. Bucci Cubo 14C, Italy. d.pucci@unical.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Pucci
authors.forename: Alessandra
authors.initials: A
authors.lastname: Crispini
authors.forename: Bárbara
authors.initials: B
authors.lastname: Sanz Mendiguchía
authors.forename: Sante
authors.initials: S
authors.lastname: Pirillo
authors.forename: Mauro
authors.initials: M
authors.lastname: Ghedini
authors.forename: Sabrina
authors.initials: S
authors.lastname: Morelli
authors.forename: Loredana
authors.initials: L
authors.lastname: De Bartolo
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D003474:Curcumin; D015032:Zinc