Non-classical anticancer agents: synthesis and biological evaluation of zinc(II) heteroleptic complexes.
New heteroleptic complexes (1-8) containing Zn(II) ion coordinated to an N,N-chelating ligand (the 4,4'-dinonyl-2,2'-bipyridine, bpy-9) and to diketonates L such as tropoloids (Tropolone and Hinokitiol) or 1-phenyl-3-methyl-4-R-5-pyrazolones have been synthesized by using different stoichiometric ratio with respect to the L ancillary ligand. The molecular structure of the bis-tropolonate derivative [(bpy-9)Zn(L)(2)] 5 has been determined by single-crystal X-ray diffraction. The antitumour activity of all Zn(II) complexes was tested in vitro against three different human prostate cancer cells: DU145, LNCaP and PC-3. Moreover, their effect on cell survival signalling and/or inhibitors of the PC-3 cell cycle have been analyzed. The results indicate that 1-8 exhibit strong cytotoxic activity against all cell lines affecting key molecules such as p-AKT and p21 waf, involved in the cell proliferation and/or arrest. Zinc(II) is thus a promising alternative to Pt(II) ion in the design of new, better performing antitumour agents.
Liguori
Paola F
PF
Centro di Eccellenza CEMIF.CAL-LASCAMM, CR-INSTM Unità della Calabria, Dipartimento di Chimica, Università della Calabria, Via P. Bucci Cubo 14C, Italy.
Valentini
Alessandra
A
Palma
Mariagrazia
M
Bellusci
Anna
A
Bernardini
Sergio
S
Ghedini
Mauro
M
Panno
Maria Luisa
ML
Pettinari
Claudio
C
Marchetti
Fabio
F
Crispini
Alessandra
A
Pucci
Daniela
D
D015082:2,2'-Dipyridyl / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008968:Molecular Conformation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015032:Zinc / Q000737:chemistry*
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015082:2,2'-Dipyridyl; D051057:Proto-Oncogene Proteins c-akt; D015032:Zinc