TY - JOUR
T1 - Synthesis, characterization and antiproliferative activity on mesothelioma cell lines of bis(carboxylato)platinum(iv) complexes based on picoplatin
AU - Ravera, Mauro
AU - Gabano, Elisabetta
AU - Zanellato, Ilaria
AU - Bonarrigo, Ilaria
AU - Escribano, Esther
AU - Moreno, Virtudes
AU - Font-Bardia, Mercè
AU - Calvet, Teresa
AU - Osella, Domenico
PY - 2012/3/21
Y1 - 2012/3/21
N2 - The synthesis and characterization of a series of picoplatin-based (picoplatin = [PtCl 2(mpy)(NH 3)], mpy = 2-methylpyridine), Pt(iv) complexes with axial carboxylato ligands of increasing length are reported. The synthesis is based on the oxidation with hydrogen peroxide of picoplatin to give the cis,cis,trans-[PtCl 2(mpy)(NH 3)(OH) 2] intermediate and then its transformation into the dicarboxylato complexes cis,cis,trans-[PtCl 2(mpy)(NH 3)(RCOO) 2] (R = CH 3(CH 2) n, n = 0-4) with the corresponding anhydride. Pt(iv) complexes with n = 0-2 were selected to be tested on four malignant pleural mesothelioma (MPM) cell lines, on human mesothelial cells (HMC), and on the cisplatin-sensitive ovarian A2780 cell line along with cisplatin as a metallo-drug reference. In general, the longer the axial chain, the more cytotoxic and selective the Pt(iv) complex is. Pt(iv) analogs show good activity on the MPM cell lines, approaching or in some case bypassing that of cisplatin and represent quite promising drug candidates for the treatment of tumors whose chemoresistance is mainly based on glutathione overexpression, such as MPM.
AB - The synthesis and characterization of a series of picoplatin-based (picoplatin = [PtCl 2(mpy)(NH 3)], mpy = 2-methylpyridine), Pt(iv) complexes with axial carboxylato ligands of increasing length are reported. The synthesis is based on the oxidation with hydrogen peroxide of picoplatin to give the cis,cis,trans-[PtCl 2(mpy)(NH 3)(OH) 2] intermediate and then its transformation into the dicarboxylato complexes cis,cis,trans-[PtCl 2(mpy)(NH 3)(RCOO) 2] (R = CH 3(CH 2) n, n = 0-4) with the corresponding anhydride. Pt(iv) complexes with n = 0-2 were selected to be tested on four malignant pleural mesothelioma (MPM) cell lines, on human mesothelial cells (HMC), and on the cisplatin-sensitive ovarian A2780 cell line along with cisplatin as a metallo-drug reference. In general, the longer the axial chain, the more cytotoxic and selective the Pt(iv) complex is. Pt(iv) analogs show good activity on the MPM cell lines, approaching or in some case bypassing that of cisplatin and represent quite promising drug candidates for the treatment of tumors whose chemoresistance is mainly based on glutathione overexpression, such as MPM.
UR - http://www.scopus.com/inward/record.url?scp=84857524516&partnerID=8YFLogxK
U2 - 10.1039/c2dt11874b
DO - 10.1039/c2dt11874b
M3 - Article
SN - 1477-9226
VL - 41
SP - 3313
EP - 3320
JO - Dalton Transactions
JF - Dalton Transactions
IS - 11
ER -