2-Benzoylpyridine-N(4)-tolyl thiosemicarbazones and their palladium(II) complexes: Cytotoxicity against leukemia cells

Abstract

The palladium(II) complexes [Pd(2Bz4oT)Cl], [Pd(2Bz4mT)Cl], and [Pd(2Bz4pT)Cl] were prepared with N(4)-ortho- (H2Bz4oT) N(4)-meta- (H2Bz4mT) and N(4)-para- (H2Bz4pT) tolyl-thiosemicarbazones derived from 2-benzoylpyridine. The free thiosemicarbazones proved to be highly cytotoxic against Jurkat, HL60 and the resistant HL60.Bcl-X(L) leukemia cell lines at nanomolar concentrations, but were much less cytotoxic to HepG2human hepatoma cells. Upon coordination to palladium(II) the cytotoxic activity against all studied cell lines decreases. However, the high cytotoxicity of the free thiosemicarbazones against leukemia, together with their hepatotoxic profile similar to that of cisplatin suggest that N(4)-tolyl thiosemicarbazones have potential as chemotherapeutic drug candidates.

Synthesis, Structural Characterization, and Pro‐apoptotic Activity of 1‐Indanone Thiosemicarbazone Platinum(II) and Palladium(II) Complexes: Potential as Antileukemic Agents

“…[32] Active compounds failed to induce cytotoxicity in HepG2 cells. Apoptosis was not induced by platinum(II) complexes but cell exposure to palladium(II) complexes increased the rate of cells undergoing the early stages of apoptosis (Figure 4 a-c).…”

Palladium(II) Complexes of NS Donor Ligands Derived from Steroidal Thiosemicarbazones as Antibacterial Agents

“…In several cases, the pharmacological action of the thiosemicarbazons is enhanced due to the presence of coordination metal ions [4,5]. It is well authenticated that a NS bidentate system is present in most of the thiosemicarbazones having carcinostatic potency and possessing substantial in vitro activity against various human tumour lines [6,7]. The thiosemicarbazone derivatives of Pd(II) have proven to be more effective as anticancer or anti-microbial agents than the ligand by itself , probably due to the increased lipophilicity of the complexes as compared to the free ligands alone [8].…”

Palladium(II) and Antimony(III) Complexes Derived From 2-Benzoylpyridine N4-Phenylthiosemicarbazone: Synthesis, Crystal Structure, Antiproliferative Activity, and Low Toxicity on Normal Hepatocyte QSG7701 Cells

“…All the bond lengths fall in the range of reported values. [27] The shortening of the bond lengths of the Pd-N (imine), relative to the bond distances of the Pd-N(pyridine), may be attributed to the fact that the imine nitrogen is a stronger base compared with the pyridine nitrogen. [28] The measured C(7)-S(1) and C(26)-S(2) bond distances of 1.755 (5) A and 1.744(5) A are within the normal range of a C-S single bond, indicating that the ligand adopted a thiol tautomeric form and acted as a mono negative ligand.…”