Palladated and platinated complexes derived from phenylacetaldehyde thiosemicarbazone with cytotoxic activity in cis-DDP resistant tumor cells. Formation of DNA interstrand cross-links by these complexes.
In the present paper we report the synthesis and characterization by 1H 13C NMR and heteronuclear 2D NMR spectroscopies of two new metallic complexes derived from phenylacetaldehyde thiosemincarbazone: Pt(C9H11N3S)Cl2, compound 2, and Pd(C9H11N3S)Cl2, compound 3. The testing of the cytotoxic activity of these compounds against several human and murine cell lines sensitive and resistant to cis-DDP suggests that compounds 2 and 3 may be considered potential anticancer agents since they exhibit 1C50 values in a microM range similar to cisplatin (cis-DDP). The cytotoxic activity of these compounds is higher in cis-DDP-resistant tumor cells than that of other antitumor drugs such as etoposide and adriamycin. On the other hand, the analysis of the interaction of compounds 2 and 3 with linear plasmid DNA indicate that both compounds, particularly compound 3, have an enhanced capacity to form DNA interstrand cross-links in comparison with cis-DDP.
Quiroga
A G
AG
Departamento de Química Inorgánica, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
Pérez
J M
JM
Montero
E I
EI
Masaguer
J R
JR
Alonso
C
C
Navarro-Ranninger
C
C
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D004317:Doxorubicin / Q000633:toxicity; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000633:toxicity; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D007202:Indicators and Reagents; D019169:Jurkat Cells; D019906:Nuclear Magnetic Resonance, Biomolecular; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D010957:Plasmids / Q000187:drug effects; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D007202:Indicators and Reagents; D009942:Organometallic Compounds; D009944:Organoplatinum Compounds; D013882:Thiosemicarbazones; C113710:dichloro(phenylacetaldehyde thiosemicarbazone)platinum(II); C113711:dichloro(phenylacetaldehyde-thiosemicarbazone)palladium(II); D005047:Etoposide; D004317:Doxorubicin; D002945:Cisplatin