In vitro effect of Pt and Pd mercaptopyridine complexes.
In previous research we studied the cytotoxic effect of new Pt mercaptopyridine (MP) complexes on several tumoral cell lines (F10, Föhn, LoVo and HeLa) as well as on the fibroblast cell line (3T3). The more interesting Pt compounds are compared here to Pd mercaptopyridine analogs, in order to evaluate the metals influence on activity. Earlier, the complexes C/2 = [Pt(MP)3Cl]Cl; C/5 = [Pt(MP)3Br]Br; C/8 = [Pd(MP)3Cl]Cl and C/11 = [Pd(MP)3Br]Br and cis-DDP as reference were tested on 3T3 and LoVo cells, by Sauter's multiwells technique and neutral red uptake. The results obtained using lysosomal neutral red uptake to confirm those by the Sauter's multiwells techniques, showing that C/2 and C/11 are the most active complexes. In particular, C/2 shows a significantly higher cytotoxic activity than cis-DDP on LoVo cells, and equivalent on 3T3. C/5 complex also induces an interesting cell growth reduction, but only on LoVo, while C/8 is completely inactive on all cell lines. Because the major limitation to the successful treatment of platinum-based chemotherapeutic regimens is the emergence of drug resistance, the activity of the four complexes on cis-DDP sensitive (M5076) and cis-DDP resistant cancer cells (M5/DDPc) has been tested. The data reported in this work make devident that the presence of ligands with sulfur donor atoms may be of particular importance in confirming the antitumor properties of Pt complexes. In fact, Pt mercaptopyridine C/2 is also more active than cis-DDP against cells made resistant to cis-DDP. Moreover, the results obtained with Pd complex C/11, especially on LoVo cells, showed that this metal could be considered interesting in the design of potential new antitumor drugs.
Carrara
M
M
Department of Parmacology Egidio Meneghetti, University of Padova, Italy.
Berti
T
T
D'Ancona
S
S
Cherchi
V
V
Sindellari
L
L
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010165:Palladium / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011725:Pyridines; D013438:Sulfhydryl Compounds; D010165:Palladium; D002945:Cisplatin