The cytostatic activity of a five-coordinate Pt(II) complex: preliminary results

The major interest in platinum(II) complexes as anticancer drugs is still centered at present on square complexes and mainly on cisplatin. Since it was observed that the nature and/or the arrangement of the ligands can dramatically affect the relevant steps (such as crossing the cell membrane, hydrolytic processes and intrastrand DNA crosslinking) of the action and the metabolism of the drug, we were prompted to probe the cytostaticactivity of the more unusual 18e bpt complexes. We examined the behavior of PtCl(Me)(maleic acid)(o-MeC5H4NCHNMe), which is soluble in water at pH 6.8. For this complex previous experiments showed a toxicity comparable to that of cisplatin towards the lymphoid system in rat embryos. The complex was prepared by a procedure similar to that used for similar dichloro complexes by exchange of maleic acid with the corresponding ethylene complex. An in vitro system which has proved very interesting is that of neuroblastoma cells in culture. Neuroblastomas are malignant tumors with reduced sensitivity to common treatments. Then, the study of the control mechanisms of the cellular differentiation gives the possibility of transferring to the therapy the results obtained in vitro. The effect of the five-coordinate complex was compared with that of cisplatin by treatment of murine neuroblastoma cells 41A3 for 24 h at a concentration of 10−6–10−7 M. A similar cell growth inhibition was observed with both the compounds: these results were also confirmed by the inhibition of 3H-thymidine incorporation into cellular DNA. The data obtained indicate that a systematic exploration of the cytostaticactivity of five-coordinate Pt(II) complexes is of potential interest.