It is known that metallic complexes of methyl 2-pyridyl ketone thiosemicarbazone (HL 1) and p-isopropyl benzaldehyde thiosemicarbazone (HL 2) may have potential antitumor activity. We have prepared complexes of HL 1 and HL 2 with Zn(II) and Cd(II). The cytotoxic activity shown by these compounds against cell lines sensitive and resistant to cis-diamminedichloroplatinum(II) ( cis-DDP) indicates that coupling of HL 1 and HL 2 to Zn(II) and Cd(II) centers may result in metallic complexes with important biological properties since they display IC 50 values in a μM range similar to that of the antitumor drug cis-DDP. Moreover, it is interesting to note that the Zn/HL 2 complex exhibits specific cytotoxic activity against Pam- ras cells ( cis-DDP resistant cells which overexpress the H- ras oncogene) with an in vitro therapeutic index of 3.26 versus 0.78 for cis-DDP. Treatment of Pam- ras cells with the IC 50 value of the Zn/HL 2 compound induces a ‘DNA ladder’ (fragmentation of genomic DNA in nucleosome units) indicative of apoptosis in this ras-transformed cell line. In contrast, a ‘DNA smear' (non-specific fragmentation of genomic DNA) is observed in Pam 212 normal cells treated with the IC 50 of this compound. The analysis by circular dichroism (CD) spectroscopy of the interaction of the Zn/HL 2 compound with calf thymus DNA (CT DNA) indicates that it produces stronger alterations on the double helix conformation than cis-DDP. So, these results suggest that Zn/HL 2 may be considered a potential antitumor agent.