Synthesis, characterization and biological activity of platinum(II) complexes with a tetrapyrazole ligand

Higuera-Padilla, Ángel R.; Capote, Jorlis; Ortega, Dianela; Castro, William; Rodriguez-Cordero, Mildred; Coll, David S.; Hernández-Medina, Fernando; Fernández‐Mestre, Mercedes; Urdanibia, Izaskun; Taylor, Peter; Rodríguez, Bárbara; Karam, Arquı́medes

doi:10.1016/j.poly.2015.09.065

Cited by 11 publications

(2 citation statements)

References 52 publications

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“…Recent studies revealed that thioredoxin reductase (TrxR) plays an important role in regulating the redox balance and intracellular signaling pathways, which made it a potential target for cancer treatment. − For instance, alkynyl phosphine gold complex displays strong inhibitory effect on TrxR activities and proliferation of cancer cells. Curcumin, daily consumed by millions of people, exhibited potent irreversible inhibition on TrxR activity in a dose- and time-dependent manner. , Although a great number of complexes (mostly gold compounds) have been reported to exhibit TrxR inhibition and antiproliferative properties, iron complexes were rarely taken in consideration in this area. − Frontier researches have demonstrated that the biological response with TrxR was mainly dependent on the chelate ability of the ligand on the complex, causing different rates of ligand-exchange of the complex . However, high binding affinity of Fe(II/III) complexes with a thiol group may result in their easy binding with blood thiols, including glutathione (GSH) and albumin (BSA), which limited its bioavailability to cancer cells. − Therefore, minimizing the binding rate between blood thiols and Fe(II/III) complexes but maintaining its inhibition activity to TrxR is important in the design of new anticancer complexes.…”

Section: Introductionmentioning

confidence: 99%

Anticancer and Antiangiogenic Iron(II) Complexes That Target Thioredoxin Reductase to Trigger Cancer Cell Apoptosis

et al. 2016

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Thioredoxin reductase (TrxR) is a selenoenzyme that could regulate intracellular oxidative balance and found to be overexpressed in many human tumor cells. Due to its important role in cancer progression, TrxR is becoming an attractive target in chemotherapeutic drug design. In this study, a new class of Fe(II) complexes with phenanthroline derivatives as ligands were synthesized and characterized. The mechanism of cell death induced by complex 3 revealed that the growth of cancer cells was suppressed by apoptosis and specifically inhibited the activities of TrxR. Furthermore, complex 3 exhibited brilliant antiangiogenic activity against HUVEC cells and inhibited cell migration and invasion. In addition, results of hematological analysis and H&E staining demonstrated that complex 3 has negligible toxicity on function of the major organs of mice. Taken together, this study provides a strategy for drug design to exploit Fe-based phenanthroline derivative as a chemotherapeutic agent in cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Anticancer and Antiangiogenic Iron(II) Complexes That Target Thioredoxin Reductase to Trigger Cancer Cell Apoptosis

et al. 2016

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“…The temperature versus absorbance curves were obtained from the equipment software in the range of 40 to 90 °C with a heating ramp of 1 °C/min and with average intervals of one minute. The melting temperature results were expressed as differences from the Tm CT-DNA alone [ 49 ].…”

Section: Methodsmentioning

confidence: 99%

Copper (I)-Chloroquine Complexes: Interactions with DNA and Ferriprotoporphyrin, Inhibition of β-Hematin Formation and Relation to Antimalarial Activity

et al. 2022

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A new Cu(I)-chloroquine (CQ) complex [Cu(CQ)(PPh3)2]NO3 (1) was synthesized and characterized, and its mechanism of action studied concomitant with the previously reported complex [Cu(CQ)2]Cl (2). These copper (I) coordination compounds can be considered as potential antimalarial agents because they show better inhibition of the CQ-resistant strain in in vitro studies than CQ alone. In comparison with other metal-CQ complexes, only the gold complex was similar to (1), i.e., more active than CQ against both CQ-susceptible (3D7) and CQ-resistant strains (W2). These two copper (I)-compounds also demonstrated higher antiplasmodial activity against W2 than other copper complexes reported to date. This suggests that the incorporation of the copper metal center enhanced the biological activity of CQ. To better understand their significant growth inhibition of the Plasmodium falciparum parasite, the interaction with two essential molecular targets for the survival and proliferation of the malarial parasite were studied. These were the ferriprotoporphyrin group and the DNA, both important targets for current antimalarial drugs at the asexual erythrocytic stages. Both compounds (1,2) exhibited significant interactions with these targets. In particular, interactions with the DNA were dominated by the intercalator properties of the CQ ligand but may have also been affected by the presence of copper. Overall, these compounds were better parasitic inhibitors than chloroquine diphosphate (CQDP) alone or other previously reported metal-CQ complexes such as platinum, ruthenium and gold.

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Characterization of new Pt(IV)–thiazole complexes: Analytical, spectral, molecular modeling and molecular docking studies and applications in two opposing pathways

Althagafi

El‐Metwaly

Farghaly

2019

Applied Organom Chemis

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New thiazole derivatives were synthesized and fully characterized, then coordinated with PtCl4 salt. Also, the newly synthesized Pt(IV) complexes were investigated analytically (elemental and thermogravimetric analyses), spectrally (infrared, UV–visible, mass, 1H NMR, 13C NMR, X‐ray diffraction) as well as theoretically (kinetics, modeling and docking). The data extracted led to the establishment of the best chemical and structural forms. Octahedral geometry was the only formula proposed for all complexes, which is favorable for d6 systems. The molecular ion peaks from mass spectral analysis coincide with all analytical data, confirming the molecular formula proposed. X‐ray diffraction (XRD) and scanning electron microscopy (SEM) allowed discrimination of features between crystalline particles and other amorphous morphology. By applying Gaussian09 as well as HyperChem 8.2 programs, the best structural forms were obtained, as well as computed significant parameters. Computed parameters such as softness, hardness, surface area and reactivity led us towards application in two opposing pathways: tumor inhibition and oxidation activation. The catalytic oxidation for CO was conducted over PtO2, which was yielded from calcination of the most reactive complex. The success of catalytic role for synthesized PtO2 was due to its particulate size and surface morphology, which were estimated from XRD patterns and SEM images, respectively. The antitumor activity was tested versus HCT‐116 and HepG‐2 cell lines. Mild toxicity was recorded for two of the derivatives and their corresponding complexes. This degree of toxicity is more favorable in most cases, due to exclusion of serious side effects, which is coherently attached with known antitumor drugs.

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Synthesis, characterization and biological activity of platinum(II) complexes with a tetrapyrazole ligand

Cited by 11 publications

References 52 publications

Anticancer and Antiangiogenic Iron(II) Complexes That Target Thioredoxin Reductase to Trigger Cancer Cell Apoptosis

Anticancer and Antiangiogenic Iron(II) Complexes That Target Thioredoxin Reductase to Trigger Cancer Cell Apoptosis

Copper (I)-Chloroquine Complexes: Interactions with DNA and Ferriprotoporphyrin, Inhibition of β-Hematin Formation and Relation to Antimalarial Activity

Characterization of new Pt(IV)–thiazole complexes: Analytical, spectral, molecular modeling and molecular docking studies and applications in two opposing pathways

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