TY - JOUR
T1 - Cytotoxic gold compounds
T2 - Synthesis, biological characterization and investigation of their inhibition properties of the zinc finger protein PARP-1
AU - Serratrice, Maria
AU - Edafe, Fabio
AU - Mendes, Filipa
AU - Scopelliti, Rosario
AU - Zakeeruddin, Shaik Mohammed
AU - Grätzel, Michael
AU - Santos, Isabel
AU - Cinellu, Maria Agostina
AU - Casini, Angela
PY - 2012/3/21
Y1 - 2012/3/21
N2 - The new gold(iii) complexes: [Au{2-(2′-pyridyl)imidazolate}Cl 2] and [Au{2,6-bis(2′-benzimidazolate)pyridine}(OCOCH 3)] and the mono- and binuclear gold(i) complexes: [Au{2-(2′-pyridyl)imidazole}(PPh 3)](PF 6), [Au(2-phenylimidazolate)(DAPTA)] (DAPTA = 3,7-diacetyl-1,3,7-triaza-5- phosphabicyclo[3.3.1]nonane), [(PPh 3Au) 2(2-R-imidazolate)] (PF 6) (R = 2-C 5H 4N, Ph) have been synthesized and characterized. The structure of the [(PPh 3Au) 2{2- (2′-pyridyl)imidazolate)](PF 6) complex was also characterized by X-ray crystallography. The antiproliferative properties of the complexes were assayed against human ovarian carcinoma cell lines, either sensitive (A2780) or resistant to cisplatin (A2780cisR), human mammary carcinoma cells (MCF7) and non-tumorigenic human kidney (HEK293) cells. Most of the studied compounds showed important cytotoxic effects. Interestingly, the compounds containing the 2-(2′-pyridyl)imidazolate ligand showed selectivity towards cancer cells with respect to the non-tumorigenic ones, with the dinuclear compound [(PPh 3Au) 2{2-(2′-pyridyl)imidazolate)](PF 6) being the most active. Some compounds were also screened for their inhibitory effect of the zinc-finger protein PARP-1, essential for DNA repair and relevant to the mechanisms of cancer cell resistance to cisplatin. Interaction studies of the compounds with the model protein ubiquitin were undertaken by electrospray ionization mass spectrometry (ESI MS). The results are discussed in relation to the putative mechanisms of action of the cytotoxic gold compounds.
AB - The new gold(iii) complexes: [Au{2-(2′-pyridyl)imidazolate}Cl 2] and [Au{2,6-bis(2′-benzimidazolate)pyridine}(OCOCH 3)] and the mono- and binuclear gold(i) complexes: [Au{2-(2′-pyridyl)imidazole}(PPh 3)](PF 6), [Au(2-phenylimidazolate)(DAPTA)] (DAPTA = 3,7-diacetyl-1,3,7-triaza-5- phosphabicyclo[3.3.1]nonane), [(PPh 3Au) 2(2-R-imidazolate)] (PF 6) (R = 2-C 5H 4N, Ph) have been synthesized and characterized. The structure of the [(PPh 3Au) 2{2- (2′-pyridyl)imidazolate)](PF 6) complex was also characterized by X-ray crystallography. The antiproliferative properties of the complexes were assayed against human ovarian carcinoma cell lines, either sensitive (A2780) or resistant to cisplatin (A2780cisR), human mammary carcinoma cells (MCF7) and non-tumorigenic human kidney (HEK293) cells. Most of the studied compounds showed important cytotoxic effects. Interestingly, the compounds containing the 2-(2′-pyridyl)imidazolate ligand showed selectivity towards cancer cells with respect to the non-tumorigenic ones, with the dinuclear compound [(PPh 3Au) 2{2-(2′-pyridyl)imidazolate)](PF 6) being the most active. Some compounds were also screened for their inhibitory effect of the zinc-finger protein PARP-1, essential for DNA repair and relevant to the mechanisms of cancer cell resistance to cisplatin. Interaction studies of the compounds with the model protein ubiquitin were undertaken by electrospray ionization mass spectrometry (ESI MS). The results are discussed in relation to the putative mechanisms of action of the cytotoxic gold compounds.
UR - http://www.scopus.com/inward/record.url?scp=84857563583&partnerID=8YFLogxK
U2 - 10.1039/c2dt11913g
DO - 10.1039/c2dt11913g
M3 - Article
C2 - 22289927
AN - SCOPUS:84857563583
SN - 1477-9226
VL - 41
SP - 3287
EP - 3293
JO - Dalton Transactions
JF - Dalton Transactions
IS - 11
ER -
