In vitro and in vivo evaluation of organometallic gold(<scp>i</scp>) derivatives as anticancer agents

Garcia-Moreno, E.B.; Tomás, Alejandro Caamaño; Atrián‐Blasco, Elena; Gascón, Sonia; Romanos, Eduardo; Rodriguez-Yoldi, Mary Jesus; Cerrada, Elena; Laguna, Mariano

doi:10.1039/c5dt01802a

Cited by 44 publications

(35 citation statements)

References 86 publications

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“…2B). The value obtained in the experiment for the binding constant at room temperature of 7.21·10 4 M − 1 is notably higher than the measured in the interaction of cisplatin with HSA 8.52·10 2 M − 1 [48] and in related alkyne gold(I) derivatives (values ranging from 10 1 to 10 3 ) [49], but is next to the values found in the anion [Au(CN) 2 ] − [50] and in gold(III) complexes (10 4 -10 5 ) [51,52], although significantly smaller than the observed in gold nanoparticles (around 10 8 -10 10 ) [53,54]. The experimental value of K b of 7.21·10 4 M − 1 is in accordance with a significant interaction with BSA, which would allow the biodistribution of the drug in plasma.…”

Section: Interaction With Bsamentioning

confidence: 52%

The anticancer effect related to disturbances in redox balance on Caco-2 cells caused by an alkynyl gold(I) complex

Sánchez-de-Diego

Mármol

Pérez

et al. 2017

Journal of Inorganic Biochemistry

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The alkynyl gold(I) derivative [Au(C≡CPh)(PTA)] (PTA=1,3,5-triaza-7-phosphaadamantane) induces apoptosis in colorectal carcinoma tumour cells (Caco-2) without affecting to normal enterocytes. [Au(C≡CPh)(PTA)] is a slight lipophilic drug, stable in PBS (Phosphate Buffered Saline) and able to bind BSA (Bovin Serum Albumin) by hydrophobic interactions. Once inside the cell, [Au(C≡CPh)(PTA)] targets seleno proteins such as Thioredoxin Reductase 1, increasing ROS (Reactive Oxygen Species) levels, reducing cell viability and proliferation and inducing mitochondrial apoptotic pathway, pro-apoptotic and anti-apoptotic protein imbalance, loss of mitochondrial membrane potential, cytochrome c release and activation of caspases 9 and 3. Moreover, unlike other metal-based drugs such as cisplatin, [Au(C≡CPh)(PTA)] does not target nucleic acid, reducing the risk of side mutation in the DNA. In consequence, our results predict a promising future for [Au(C≡CPh)(PTA)] as a chemotherapeutic agent for colorectal carcinoma.

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Section: Interaction With Bsamentioning

confidence: 52%

The anticancer effect related to disturbances in redox balance on Caco-2 cells caused by an alkynyl gold(I) complex

Sánchez-de-Diego

Mármol

Pérez

et al. 2017

Journal of Inorganic Biochemistry

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“…One of the purposes of cancer chemotherapy is fight against malignant cells in one or more stages of the reproductive cycle . Because the cytotoxicity of metal‐based drugs is usually linked with cell cycle perturbation, cell cycle analysis was performed after treating A549 cells with 3C at 0.5, 1 and 2 equipotent concentrations of IC 50 for 24 h (Figure ; and Table S1 in the supporting information).…”

Section: Resultsmentioning

confidence: 99%

Lysosome‐targeted potent half‐sandwich iridium(III) α‐diimine antitumor complexes

Kong

Guo

Tian

et al. 2018

Applied Organom Chemis

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Fifteen organometallic Ir(III) half-sandwich complexes (1A-5C) having the general formula [(η 5 -Cp x )Ir(N^N)Cl]PF 6 (Cp x = Cp*, tetramethyl(phenyl) cyclopentadienyl (Cp xph ) or tetramethyl(biphenyl)cyclopentadienyl (Cp xbiph ); N^N = diamine) have been synthesized and characterized. The molecular structure of 1A was determined using single-crystal X-ray diffraction analysis.The hydrolysis of 1A-5C was monitored using UV-visible spectra. Complexes 3A-3C showed catalytic activity for the oxidation of NADH to NAD + , where 3C showed the highest turnover number of 29.9 within 450 min. Cytotoxicity examination by MTT assay was carried out against two human cancer cell lines (HeLa and A549) after 24 or 48 h drug treatment. The complexes showed high potency, where the most potent complex (3C; IC 50 = 3.4 μM) was six times more active than cisplatin against A549 cells after 24 h drug exposure. Cytotoxic potency towards A549 cells increased with phenyl substitution on Cp ring: Cp xbiph > Cp xph > Cp*. In addition, the biological studies showed that 3C caused cell apoptosis and cell cycle arrest at G 1 phase in A549 cancer cells.Moreover, 3C increased the level of reactive oxygen species markedly after 24 h, which may provide an important basis for killing cancer cells. Confocal laser scanning microscopy was used to track 3C in A549 cells. The cellular localization experiment showed that 3C targeted lysosomes and caused lysosomal damage.

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“…In this regard, PTA (1,3,5‐triaza‐7‐phosphaadamantane) and its derivatives are the most widely employed ligands for improving the water solubility of metallic complexes . Some of these compounds have displayed promising anticancer activity against primary, , and metastatic tumours , …”

Section: Introductionmentioning

confidence: 99%

Synthesis of Gold(I) Derivatives Bearing Alkylated 1,3,5‐Triaza‐7‐phosphaadamantane as Selective Anticancer Metallodrugs

et al. 2016

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The alkylation of one of the nitrogen atoms of the molecule 1,3,5,triaza‐7‐phosphaadamantane (PTA) with para‐substituted benzylic units and the l‐phenylalanine methyl ester moiety are reported. The crystalline structures of the two alkylated PTA species [PTA‐CH2‐p‐COOH‐C6H4]Br (1a) and [PTA‐CH2‐p‐CH2COOH‐C6H4]Br (2) reveal the presence of interactions between the bromide anion and the OH group of the acid moiety. Bis‐phosphane derivatives were prepared by the alkylation of two PTA molecules with a dibromide salt to afford more water‐soluble species. The corresponding mono‐ and dinuclear chloro‐, thiocyanato‐ and pentafluorophenyl gold(I) derivatives are described. Most of the new complexes have been tested as anticancer agents, exhibiting higher cytotoxicity than cisplatin against human colon cancer cell lines. Some of them display low cytotoxicity towards differentiated cells (non‐carcinogenic), as determined from viability studies, thereby demonstrating a significant specificity in this type of cancer.

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In vitro and in vivo evaluation of organometallic gold(i) derivatives as anticancer agents

Abstract: Alkyne gold(i) derivatives with the water soluble phosphanes PTA and DAPTA were described and their anticancer potential against the colon cancer cell line Caco-2 (PD7 and TC7 clones) was studied.

Cited by 44 publications

References 86 publications

The anticancer effect related to disturbances in redox balance on Caco-2 cells caused by an alkynyl gold(I) complex

The anticancer effect related to disturbances in redox balance on Caco-2 cells caused by an alkynyl gold(I) complex

Lysosome‐targeted potent half‐sandwich iridium(III) α‐diimine antitumor complexes

Synthesis of Gold(I) Derivatives Bearing Alkylated 1,3,5‐Triaza‐7‐phosphaadamantane as Selective Anticancer Metallodrugs

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