The palladium(II) bis-chelate complexes of the type [Pd(TSC1-5)2] (6–10), with their corresponding ligands 4-phenyl-1-(acetone)-thiosemicarbazone, HTSC1 (1), 4-phenyl-1-(2′-chloro-benzaldehyde)-thiosemicarbazone, HTSC2 (2), 4-phenyl-1-(3′-hydroxy-benzaldehyde)-thiosemicarbazone, HTSC3 (3), 4-phenyl-1-(2′-naphthaldehyde)-thiosemicarbazone, HTSC4 (4), and 4-phenyl-1-(1′-nitro-2′-naphthaldehyde)-thiosemicarbazone, HTSC5 (5), were synthesized and characterized by elemental analysis and spectroscopic techniques (IR and 1H- and 13C-NMR). The molecular structure of HTSC3, HTSC4, and [Pd(TSC1)2] (6) have been determined by single crystal X-ray crystallography. Complex 6 shows a square planar geometry with two deprotonated ligands coordinated to through the azomethine nitrogen and thione sulfur atoms in a cis arrangement. The in vitro cytotoxic activity measurements indicate that the palladium(II) complexes ( –9.87？ M) exhibited higher antiproliferative activity than their free ligands ( –70.86 and >250？ M) against different types of human tumor cell lines. Among all the studied palladium(II) complexes, the [Pd(TSC3)2] (8) complex exhibited high antitumor activity on the DU145 prostate carcinoma and K562 chronic myelogenous leukemia cells, with low values of the inhibitory concentration (0.01 and 0.02？ M, resp.). 1. Introduction In recent years, sulfur containing ligands such as dithiocarbamates and thiosemicarbazones and their transition metal complexes have received more attention in the area of medicinal chemistry, due to their pharmacological properties, such as antiviral [1–3], antibacterial [4–7], antifungal [8–10], antiparasitic [11, 12], and antitumor [13–19] activities. The synthesis of thiosemicarbazones (R–CH=N–NH–CS–NHR1) has been developed due to the facility to replace the R and R1 substituent groups by alkyl, aryl, or heterocyclic derivative and thus leading to a broad spectrum of new bidentate (N,S or N,N) and tridentate (N,N,N or N,N,S) and also tetra- and pentadentate ligands, capable of coordinating to metal centres [6, 20–22]. It has been shown that the α-(N)-heterocyclic carbaldehyde thiosemicarbazones act as chelating agents of the transition metals and some of them exhibit antitumor activity by inhibiting the biosynthesis of DNA, possibly by blocking the enzyme ribonucleotide diphosphate reductase [23–25]. On the other hand, the ligand 6-methylpyridine-2-carbaldehyde-N(4)-ethylthiosemicarbazone (HmpETSC) and its complexes [Zn(HmpETSC)Cl2] and [Pd(mpETSC)Cl] exhibit antineoplastic activity against colon cancer human cell lines (HCT 116)
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