Abstract
New platinum(II) complexes of cyclopentanecarboxylic
acid hydrazide (cpcah) were prepared, characterized
by elemental analysis, IR and 1H 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
carcinoma. The spectral analyses indicated a cissquare
planar structure of the complexes with hydrazide
ligand coordinated via the NH2 group. The
compounds exerted significantly lower in vitro and
in vivo toxicities as compared with those of cisplatin
(cis-diamminedichloroplatinum(II), DDP). On the other
hand, the complex [Pt(NH3)(cpcah)Cl2] exhibited antitumor
activity against L1210 leukemia in mice comparable
to that of cisplatin, resulting at a dose 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 pattern
similar to that of DDP. At concentrations close to the
cytostatic ones (10–20 μM) this complex, as well as
DDP, was able to induce apoptosis in FL cells as shown
by neutral comet assay and morphological analysis.
We concluded that there is a correlation between the
ability of platinum complexes to induce apoptosis and
their antitumor activity.
