Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines

Abstract

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 PdII through the azomethine nitrogen and thione sulfur atoms in a cis arrangement. The in vitro cytotoxic activity measurements indicate that the palladium(II) complexes (IC50 = 0.01–9.87 μM) exhibited higher antiproliferative activity than their free ligands (IC50 = 23.48–70.86 and >250 μM) 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 μM, resp.).

Substituted 4-Acyl-5-methyl-2-phenyl-pyrazol-3-one-phenylhydrazones with Antioxidant Properties: X-Ray Crystal and Spectroscopic Studies

“…In the 13 C NMR spectra of synthesized compounds, Figure 3, carbon atoms due to keto C=O and azomethine C=N groups display resonance signals at 165.5 and 147.4 ppm in Empp-Ph and Prmpp-Ph, respectively [24]. Also the signals due to aromatic carbon are observed as multiplets and resonate in the chemical shift range of 147.4 and 112.9 ppm.…”

Synthesis, characterization and cytotoxic activity of tioconazole coordination compounds with nickel(II), palladium(II) and platinum(II)

“…When designing new antitumor agents, the similarity in the chemistry of the Pt II and Pd II compounds has led to the study of palladium antitumor drugs with high activity. [22][23][24][25][26] Some of them are stabilized by chelates, as Schiff bases, or by voluminous ligands with monodentate nitrogen atoms, [22] which presented activity in HeLa cell line. It has been reported that trans-Pd compounds with Schiff base ligands have better activity than the cis-Pd compounds.…”

Cytotoxic effect of palladium (II) inclusion compounds in beta-cyclodextrin

“…Las tiosemicarbazonas son una clase importante de ligandos con átomos donadores de electrones, como el azufre y el nitrógeno, que actúan como agentes quelantes de metales de transición (10) y exhiben actividad antineoplásica (5,11,12). De hecho, las tiosemicarbazonas y sus complejos metálicos son de gran interés por su amplio rango de efectos biológicos (13,14), ya que tanto los ligandos derivados de ellas como los complejos metálicos de transición tienen otras propiedades farmacológicas antivirales, antibacterianas, antifún-gicas, antiparasitarias y antitumorales (3,10,(15)(16)(17)(18).…”

“…De hecho, las tiosemicarbazonas y sus complejos metálicos son de gran interés por su amplio rango de efectos biológicos (13,14), ya que tanto los ligandos derivados de ellas como los complejos metálicos de transición tienen otras propiedades farmacológicas antivirales, antibacterianas, antifún-gicas, antiparasitarias y antitumorales (3,10,(15)(16)(17)(18).…”

“…A pesar de que la actividad citotóxica in vitro de los complejos de paladio (II) y las tiosemicarbazonas es mayor que la de sus respectivos ligandos, las dosis requeridas para lograr el efecto inhibitorio deseado en las células tumorales es muy variable y depende de la línea tumoral utilizada, por lo que se reportan rangos en las concentraciones inhibitorias que van de 0,08 a 38 µM para los complejos de paladio (II) y de 23 a 250 µM para las tiosemicarbazonas (9,10,12,15,22). En el caso de las células de cáncer de mama, por ejemplo la línea celular humana de adenocarcinoma de mama MCF-7, los complejos de paladio (II) y las tiosemicarbazonas muestran mayor actividad citotóxica; sin embargo, con estas se requieren concentraciones relativamente superiores para alcanzar la dosis inhibitoria deseada.…”