Hydroxyquinoline-derived anticancer organometallics: Introduction of amphiphilic PTA as an ancillary ligand increases their aqueous solubility

Tremlett, William D.J.; Tong, Kelvin K. H.; Steel, Tasha R.; Movassaghi, Sanam; Hanif, Muhammad; Jamieson, Stephen M.F.; Söhnel, Tilo; Hartinger, Christian G.

doi:10.1016/j.jinorgbio.2019.110768

Cited by 35 publications

(19 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both enantiomers were found in the molecular structures which were overall very similar to those of the analogous complexes with hexafluorophosphate as the counterion ( Table 1 ). The M–Cp* centroid distance in 2a Cl , however, was significantly shorter than found for the Cp* complexes [ 43 ].…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…One of the most prominent compounds is the Ga(III) complex of HQ (tris(8-quinolinolato)gallium, KP46), which had successfully entered clinical trials and it was effective against renal cancer [23]. HQ and its derivatives also form complexes with Ru(η 6 -p-cymene) (RuCym) and Rh(η 5 -C 5 Me 5 ) (RhCp*) characterized by high solution stability, and many of them were reported to display potent anticancer activity in human cancer cell lines [7][8][9][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

8-Hydroxyquinoline-Amino Acid Hybrids and Their Half-Sandwich Rh and Ru Complexes: Synthesis, Anticancer Activities, Solution Chemistry and Interaction with Biomolecules

Pivarcsik

Dömötör

Mészáros

et al. 2021

IJMS

View full text Add to dashboard Cite

Solution chemical properties of two novel 8-hydroxyquinoline-D-proline and homo-proline hybrids were investigated along with their complex formation with [Rh(η5-C5Me5)(H2O)3]2+ and [Ru(η6-p-cymene)(H2O)3]2+ ions by pH-potentiometry, UV-visible spectrophotometry and 1H NMR spectroscopy. Due to the zwitterionic structure of the ligands, they possess excellent water solubility as well as their complexes. The complexes exhibit high solution stability in a wide pH range; no significant dissociation occurs at physiological pH. The hybrids and their Rh(η5-C5Me5) complexes displayed enhanced cytotoxicity in human colon adenocarcinoma cell lines and exhibited multidrug resistance selectivity. In addition, the Rh(η5-C5Me5) complexes showed increased selectivity to the chemosensitive cancer cells over the normal cells; meanwhile, the Ru(η6-p-cymene) complexes were inactive, most likely due to arene loss. Interaction of the complexes with human serum albumin (HSA) and calf-thymus DNA (ct-DNA) was investigated by capillary electrophoresis, fluorometry and circular dichroism. The complexes are able to bind strongly to HSA and ct-DNA, but DNA cleavage was not observed. Changing the five-membered proline ring to the six-membered homoproline resulted in increased lipophilicity and cytotoxicity of the Rh(η5-C5Me5) complexes while changing the configuration (L vs. D) rather has an impact on HSA or ct-DNA binding.

show abstract

“…Nevertheless, research on cyclometalated rhodium complexes has largely focused on non‐cyclopentadienyl cyclometalated rhodium complexes that target DNA, enzyme or protein–protein interfaces , , . Reported cyclopentadienyl rhodium anticancer complexes to date, have mainly contained N ^ N,, N ^ S, N ^ O, or O ^ O, , chelating ligands.…”

Section: Introductionmentioning

confidence: 99%

Ligand‐Controlled Reactivity and Cytotoxicity of Cyclometalated Rhodium(III) Complexes

et al. 2019

View full text Add to dashboard Cite

We report the synthesis, characterization and cytotoxicity of six cyclometalated rhodium(III) complexes [CpXRh(C^N)Z]0/+, in which CpX = Cp*, Cpph, or Cpbiph, C^N = benzo[h]quinoline, and Z = chloride or pyridine. Three X‐ray crystal structures showing the expected “piano‐stool” configurations have been determined. The chlorido complexes hydrolyzed faster in aqueous solution, and reacted preferentially with 9‐ethyl guanine or glutathione compared to their pyridine analogues. The 1‐biphenyl‐2,3,4,5‐tetramethylcyclopentadienyl complex [CpbiphRh(benzo‐[h]quinoline)Cl] (3a) was the most efficient catalyst in coenzyme reduced nicotinamide adenine dinucleotide (NADH) oxidation to NAD+ and induced an elevated level of reactive oxygen species (ROS) in A549 human lung cancer cells. The pyridine complex [CpbiphRh(benzo[h]quinoline)py]+ (3b) was the most potent against A549 lung and A2780 ovarian cancer cell lines, being 5‐fold more active than cisplatin towards A549 cells, and acted as a ROS scavenger. This work highlights a ligand‐controlled strategy to modulate the reactivity and cytotoxicity of cyclometalated rhodium anticancer complexes.

show abstract

Hydroxyquinoline-derived anticancer organometallics: Introduction of amphiphilic PTA as an ancillary ligand increases their aqueous solubility

Cited by 35 publications

References 52 publications

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

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

8-Hydroxyquinoline-Amino Acid Hybrids and Their Half-Sandwich Rh and Ru Complexes: Synthesis, Anticancer Activities, Solution Chemistry and Interaction with Biomolecules

Ligand‐Controlled Reactivity and Cytotoxicity of Cyclometalated Rhodium(III) Complexes

Contact Info

Product

Resources

About