Cytotoxicity of cis-platinum(II) cycloaliphatic amidine complexes: Ring size and solvent effects on the biological activity.
A series of new platinum(II) amidine derivatives of the type cis-[PtCl(2){Z-NHC(NHR)Me}(2)] (R=cyclopropyl, 1; cyclopentyl, 2; cyclohexyl, 3) were prepared in high yield by addition of the corresponding cyclic aliphatic amine RNH(2) to the coordinated acetonitrile ligands in cis-[PtCl(2)(NCMe)(2)]. The solution behaviour of 1-3 has been studied in DMSO, PEG 400 (polyethylene glycol) and PEG-DME 500 (polyethylene glycol dimethylether). The amidine complexes 1-3 were evaluated for their cytotoxic properties against a panel of human tumor cell lines containing examples of cervix (HeLa), breast (MCF7), lung (A549) and colon (HCT-15) cancer. Moreover, the amidine complexes were tested for their cytotoxicity against normal human fibroblasts (HFF-1). For comparison purposes, the cytotoxicity of cisplatin was examined under the same experimental conditions. The results obtained showed that PEG and PEG-DME behave as good solvents to carry out biological assays with platinum complexes which are water-insoluble and unstable in DMSO. Complexes 2 and 3 exhibited a biological activity comparable to that of cisplatin.
Marzano
Cristina
C
Department of Pharmaceutical Sciences, University of Padova, Italy.
Sbovata
Silvia Mazzega
SM
Gandin
Valentina
V
Michelin
Rino A
RA
Venzo
Alfonso
A
Bertani
Roberta
R
Seraglia
Roberta
R
D000578:Amidines / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D012996:Solutions; D012997:Solvents / Q000737:chemistry*
D000578:Amidines; D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D012996:Solutions; D012997:Solvents; D002945:Cisplatin