Synthesis, cytotoxicity and antitumor activity of platinum(II) complexes of cyclopentanecarboxylic acid hydrazide

New platinum(II) complexes of cyclopentanecarboxylic acid hydrazide (cpcah) were prepared, characterized by elemental analysis, IR and H-1 NMR spectra , and evaluated for in vitro cytotoxicity in Friend leukemia (FL) and A2780 ovarian tumor cells, induction of apoptosis in FL cells, as well as for in vivo antitumor activity toward murine L1210 leukemia and Lewis lung carcin oma. The spectral analyses indicated a cis-square planar structure of the c omplexes with hydrazide ligand coordinated via the NH2 group. The compounds exerted significantly lower in vitro and in vivo toxicities as compared wi th those of cisplatin (cis-diamminedichloroplatinum(II), DDP). On the other hand, the complex [Pt(NH3)(cpcah)Cl-2] exhibited antitumor activity agains t L1210 leukemia in mice comparable to that of cisplatin, resulting at a do se of 42 mg/kg (administered 3 times) in a T/C (mean survival time) of 280% . This compound displayed an in vitro macromolecular synthesis inhibition p attern similar to that of DDP. At concentrations close to the cytostatic on es (10-20 mu M) this complex, as well as DDP was able to induce apoptosis i n FL cells as shown by neutral comet assay and morphological analysis. We c oncluded that there is a correlation between the ability of platinum comple xes to induce apoptosis and their antitumor activity.