IN-VITRO EFFECT OF PT AND PD MERCAPTOPYRIDINE COMPLEXES

In previous research we studied the cytotoxic effect of new Pt mercapt opyridine (MP) complexes on several tumoral cell lines (F10, Fohn, LoV o and HeLa) as well as on the fibroblast cell line (3T3). The more int eresting 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)(3)Cl]Cl; C/5 = [Pt(MP)(3)Br]Br; C/8 = [Pd(MP)( 3)Cl]Cl and C/11 = [Pd(MP)(3)Br]Br and cis-DDP as reference were teste d 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 technique, showing that C/2 and C/11 are the most active complexes. In particular, C/2 shows a sig nificantly higher cytotoxic activity than cis-DDP on LoVo cells, and e quivalent on 3T3. C/5 complex also induces an interesting cell growth reduction, but only on LoVo, while C/8 is completely inactive on all c ell lines. Because the major limitation to the successful treatment of platinum-based chemotherapeutic regimens is the emergence of drug res istance, the activity of the four complexes on cis-DDP sensitive (M507 6) and cis-DDP resistant cancer cells (M5/DDPc) has been tested. The d ata reported in this work make devident that the presence of ligands w ith sulfur donor atoms may be of particular importance in confirming t he antitumor properties of Pt complexes. In fact, Pt mercaptopyridine C/2 is also more active than cis-DDP against cells made resistant to c is-DDP. Moreover, the results obtained with Pd complex C/11, especiall y on LoVo cells, showed that this metal could be considered interestin g in the design of potential new antitumor drugs.