Thiourea-Derived Chelating Ligands and Their Organometallic Compounds: Investigations into Their Anticancer Activity

Abstract

Thiones have been investigated as ligands in metal complexes with catalytic and biological activity. We report the synthesis, characterization, and biological evaluation of a series of MII/III complexes of the general formulae [MII(cym)(L)Cl]X (cym = η6-p-cymene) or [MIII(Cp*)(L)Cl]X (Cp* = η5-pentamethylcyclopentadienyl), where X = Cl− or PF6−, and L represents heterocyclic derivatives of thiourea. The thiones feature a benzyl-triazolyl pendant and they act as bidentate ligands via N,S-coordination to the metal centers. Several derivatives have been investigated by single-crystal X-ray diffraction analysis. NMR investigations showed a counterion-dependent shift of several protons due to the interaction with the counterions. These NMR investigations were complemented with X-ray diffraction analysis data and the effects of different counterions on the secondary coordination sphere were also investigated by DFT calculations. In biological studies, the Ir benzimidazole derivative was found to accumulate in the cytoplasm and it was the most cytotoxic derivative investigated.

Anthracenyl Functionalization of Half-Sandwich Carbene Complexes: In Vitro Anticancer Activity and Reactions with Biomolecules

“…The cytotoxicity of the compounds in HCT116, SW480, NCI-H460, and SiHa cells was determined with the SRB assay, as described previously using 72 h incubation periods after adding the compounds to the plates in a series of 3-fold dilutions, containing a maximum of 0.5% DMSO at the highest concentration …”

“…The cytotoxicity of the compounds in HCT116, SW480, NCI-H460, and SiHa cells was determined with the SRB assay, as described previously using 72 h incubation periods after adding the compounds to the plates in a series of 3-fold dilutions, containing a maximum of 0.5% DMSO at the highest concentration. 70 Cell Morphological Changes. Holographic live cell images were generated with a Tomocube and an HT-2H label-free 3D imager (Tomocube, Daejeon, South Korea), which is based on an interferometer equipped with a digital micromirror device to control the illumination beam.…”

Impact of the Metal Center and Leaving Group on the Anticancer Activity of Organometallic Complexes of Pyridine-2-carbothioamide

“…GAUSSIAN 09W [ 48 ] was used to calculate the optimized ground state structures and frequencies for the different molecules by density functional theory (DFT), as described earlier [ 49 ]. The B3LYP-D3 hybrid exchange functional was used as well as a split basis set for C, H, N, S, F and Cl (6-31G(d,p)) and the transition metals iridium, osmium, rhodium, and ruthenium (SDDAll) in vacuum.…”

Advances in Anticancer Drug Discovery

“… The molecular structure of one of the chelated thiourea enantiomers found ( left ) and Ir distribution in SKOV-3 cancer cells after treatment as determined by X-ray fluorescence microscopy ( right ) [ 2 ]. …”

“…New synthesized anticancer compounds were introduced in the s-triazine Schiff base derivatives against human breast carcinoma (MCF-7) and colon cancer (HCT-116) cell lines [ 1 ], the thioureas chelated with Ru, Os, Rh and Ir as shown in Figure 1 [ 2 ], 3-carene derivatives as novel inhibitors of tyrosyl-DNA phosphodiesterase 1 (TDP1), a promising anticancer target [ 3 ], and new anthraquinones potentially targeting DNA topoisomerase [ 4 ].…”