Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Unprecedented inhibition of P-gp activity by a novel ruthenium-cyclopentadienyl compound bearing a bipyridine-biotin ligand.

ABSTRACT: Two new ruthenium complexes, [Ru(?5-Cp)(PPh3)(2,2'-bipy-4,4'-R)]+ with R?=?-CH2OH (Ru1) or dibiotin ester (Ru2) were synthesized and fully characterized. Both compounds were tested against two types of breast cancer cells (MCF7 and MDA-MB-231), showing better cytotoxicity than cisplatin in the same experimental conditions. Since multidrug resistance (MDR) is one of the main problems in cancer chemotherapy, we have assessed the potential of these compounds to overcome resistance to treatments. Ru2 showed exceptional selectivity as P-gp inhibitor, while Ru1 is possibly a substrate. In vivo studies in zebrafish showed that Ru2 is well tolerated up to 1.17?mg/L, presenting a LC50 of 5.73?mg/L at 5 days post fertilization.

SUBMITTER: Corte-Real L

PROVIDER: S-EPMC6345558 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Unprecedented inhibition of P-gp activity by a novel ruthenium-cyclopentadienyl compound bearing a bipyridine-biotin ligand.

Côrte-Real Leonor L Karas Brittany B Gírio Patrícia P Moreno Alexis A Avecilla Fernando F Marques Fernanda F Buckley Brian T BT Cooper Keith R KR Doherty Cathleen C Falson Pierre P Garcia M Helena MH Valente Andreia A

European journal of medicinal chemistry 20181212

Two new ruthenium complexes, [Ru(η5-Cp)(PPh3)(2,2'-bipy-4,4'-R)]+ with R = -CH2OH (Ru1) or dibiotin ester (Ru2) were synthesized and fully characterized. Both compounds were tested against two types of breast cancer cells (MCF7 and MDA-MB-231), showing better cytotoxicity than cisplatin in the same experimental conditions. Since multidrug resistance (MDR) is one of the main problems in cancer chemotherapy, we have assessed the potential of these compou ...[more]

PMID: 30579125

Similar Datasets

Fighting Multidrug Resistance with Ruthenium-Cyclopentadienyl Compounds: Unveiling the Mechanism of P-gp Inhibition.

Project description:The search for more effective and selective drugs to overcome cancer multidrug resistance is urgent. As such, a new series of ruthenium-cyclopentadienyl ("RuCp") compounds with the general formula [Ru(η5-C5H4R)(4,4'-R'-2,2'-bipy)(PPh3)] were prepared and fully characterized. All compounds were evaluated toward non-small cell lung cancer cells with different degrees of cisplatin sensitivity (A549, NCI-H2228, Calu-3, and NCI-H1975), showing better cytotoxicity than the first-line chemotherapeutic drug cisplatin. Compounds 2 and 3 (R' = -OCH3; R = CHO (2) or CH2OH (3)) further inhibited the activity of P-gp and MRP1 efflux pumps by impairing their catalytic activity. Molecular docking calculations identified the R-site P-gp pocket as the preferred one, which was further validated using site-directed mutagenesis experiments in P-gp. Altogether, our results unveil the first direct evidence of the interaction between P-gp and "RuCp" compounds in the modulation of P-gp activity and establish them as valuable candidates to circumvent cancer MDR.

| S-EPMC10614197 | biostudies-literature

Luminescent ruthenium(II) complex bearing bipyridine and N-heterocyclic carbene-based C?N?C pincer ligand for live-cell imaging of endocytosis.

Project description:Luminescent ruthenium(II)-cyanide complex with N-heterocyclic carbene pincer ligand C(?)N(?)C = 2,6-bis(1-butylimidazol-2-ylidene)pyridine and 2,2'-bipyridine (bpy) shows minimal cytotoxicity to both human breast carcinoma cell (MCF-7) and human retinal pigmented epithelium cell (RPE) in a wide range of concentration (0.1-500??M), and can be used for the luminescent imaging of endocytosis of the complex in these cells.

| S-EPMC4357851 | biostudies-other

A Five-Coordinate Compound with Inverted Ligand Field: An Unprecedented Geometry for Silver(III).

Project description:By using suitable synthetic procedures, we have first isolated the square-planar organosilver(III) compounds [PPh4 ][trans-(CF3 )2 AgX2 ] [X=Cl (1 a), Br (2 a)]. The geometry and stereochemistry of the chloro-derivative 1 a have been unambiguously established by single-crystal X-ray diffraction (SC-XRD) methods. Following our calculations on the relative stability of the cis-/trans-[(CF3 )2 AgX2 ]- couples (X=F, Cl, Br, I), the experimentally obtained compounds 1 a and 2 a appear to be kinetically favored stereoisomers. They display some tendency to associate an additional X- ligand affording rare five-coordinate AgIII species [(CF3 )2 AgX3 ]2- . Interestingly, compound [PPh4 ]2 [(CF3 )2 AgBr3 ] (3) has been identified by SC-XRD methods as the first AgIII derivative with trigonal symmetry in general and trigonal bipyramidal geometry in particular. This unusual five-coordinate species also exhibits inverted ligand field.

| S-EPMC9298700 | biostudies-literature

Latent ruthenium-indenylidene catalysts bearing a N-heterocyclic carbene and a bidentate picolinate ligand.

Project description:A silver-free methodology was developed for the synthesis of unprecedented N-heterocyclic carbene ruthenium indenylidene complexes bearing a bidentate picolinate ligand. The highly stable (SIPr)(picolinate)RuCl(indenylidene) complex 4a (SIPr = 1,3-bis(2-6-diisopropylphenyl)imidazolidin-2-ylidene) demonstrated excellent latent behaviour in ring closing metathesis (RCM) reaction and could be activated in the presence of a Brønsted acid. The versatility of the catalyst 4a was subsequently demonstrated in RCM, cross-metathesis (CM) and enyne metathesis reactions.

| S-EPMC4578404 | biostudies-literature

Design and Anticancer Properties of New Water-Soluble Ruthenium-Cyclopentadienyl Complexes.

Project description:Ruthenium complexes are emerging as one of the most promising classes of complexes for cancer therapy. However, their limited aqueous solubility may be the major limitation to their potential clinical application. In view and to contribute to the progress of this field, eight new water-soluble Ru(II) organometallic complexes of general formula [RuCp(mTPPMS)n(L)] [CF3SO3], where mTPPMS = diphenylphosphane-benzene-3-sulfonate, for n = 2, L is an imidazole-based ligand (imidazole, 1-benzylimidazole, 1-butylimidazole, (1-(3-aminopropyl)imidazole), and (1-(4-methoxyphenyl)imidazole)), and for n = 1, L is a bidentate heteroaromatic ligand (2-benzoylpyridine, (di(2-pyridyl)ketone), and (1,2-(2-pyridyl)benzo-[b]thiophene)) were synthesized and characterized. The new complexes were fully characterized by NMR, FT-IR, UV-vis., ESI-HRMS, and cyclic voltammetry, which confirmed all the proposed molecular structures. The antiproliferative potential of the new Ru(II) complexes was evaluated on MDAMB231 breast adenocarcinoma, A2780 ovarian carcinoma, and HT29 colorectal adenocarcinoma cell lines, showing micromolar (MDAMB231 and HT29) and submicromolar (A2780) IC50 values. The interaction of complex 6 with human serum albumin (HSA) and fatty-acid-free human serum albumin (HSAfaf) was evaluated by fluorescence spectroscopy techniques, and the results revealed that the ruthenium complex strongly quenches the intrinsic fluorescence of albumin in both cases.

| S-EPMC9321894 | biostudies-literature

Diastereoselective Synthesis and Two-Step Photocleavage of Ruthenium Polypyridyl Complexes Bearing a Bis(thioether) Ligand.

Project description:Thioethers are good ligands for photoactivatable ruthenium(II) polypyridyl complexes, as they form thermally stable complexes that are prone to ligand photosubstitution. Here, we introduce a novel symmetric chelating bis(thioether) ligand scaffold, based on 1,3-bis(methylthio)-2-propanol (4) and report the synthesis and stereochemical characterization of the series of novel ruthenium(II) polypyridyl complexes [Ru(bpy)2(L)](PF6)2 ([1]-[3](PF6)2), where L is ligand 4, its methyl ether, 1,3-bis(methylthio)-2-methoxypropane (5), or its carboxymethyl ether, 1,3-bis(methylthio)-2-(carboxymethoxy)propane (6). Coordination of ligands 4-6 to the bis(bipyridine)ruthenium center gives rise to 16 possible isomers, consisting of 8 possible ? diastereoisomers and their ? enantiomers. We found that the synthesis of [1]-[3](PF6)2 is diastereoselective, yielding a racemic mixture of the ?-(S)-eq-(S)-ax-OHeq-[Ru]2+ and ?-(R)-ax-(R)-eq-OHeq-[Ru]2+ isomers. Upon irradiation with blue light in water, [1]-[3](PF6)2 selectively substitute their bis(thioether) ligands for water molecules in a two-step photoreaction, ultimately producing [Ru(bpy)2(H2O)2]2+ as the photoproduct. The relatively stable photochemical intermediate was identified as cis-[Ru(bpy)2(?1-L)(H2O)]2+ by mass spectrometry. Global fitting of the time evolution of the UV-vis absorption spectra of [1]-[3](PF6)2 was employed to derive the photosubstitution quantum yields (?443) for each of the two photochemical reaction steps separately, revealing very high quantum yields of 0.16-0.25 for the first step and lower values (0.0055-0.0093) for the second step of the photoreaction. The selective and efficient photochemical reaction makes the photocleavable bis(thioether) ligand scaffold reported here a promising candidate for use in e.g. ruthenium-based photo-activated chemotherapy.

| S-EPMC6724527 | biostudies-literature

Ruthenium Olefin Metathesis Catalysts Bearing a Macrocyclic N-Heterocyclic Carbene Ligand: Improved Stability and Activity.

Project description:Formation of sterically hindered C-C double bonds via catalytic olefin metathesis is considered a very challenging task for Ru catalysts. This limitation led to the development of specialised catalysts bearing sterically reduced N-heterocyclic carbene (NHC) ligands that are very active in such transformations, yet significantly less stable as compared to general purpose catalysts. To decrease the small-size NHC catalysts susceptibility to decomposition, a new NHC ligand was designed, in which two sterically reduced aryl arms were tied together by a C-8 alkyl chain. The installation of this macrocyclic ligand on the ruthenium centre led to the formation of an olefin metathesis catalyst (trans-Ru6). Interestingly, this complex undergoes transformation into an isomer bearing two Cl ligands in the cis-arrangement (cis-Ru6). These two isomeric complexes exhibit similarly high thermodynamic stability, yet different application profiles in catalysis.

| S-EPMC9322543 | biostudies-literature

Ruthenium(II)-Cyclopentadienyl-Derived Complexes as New Emerging Anti-Colorectal Cancer Drugs.

Project description:Colorectal cancer (CRC) is one of the most common malignancies and one of the leading causes of cancer-related death worldwide, urging the need for new and more efficient therapeutic approaches. Ruthenium complexes have emerged as attractive alternatives to traditional platinum-based compounds in the treatment of CRC. This work aims to evaluate anti-CRC properties, as well as to identify the mechanisms of action of ruthenium complexes with the general formula [Ru(η5-C5H4R)(PPh3)(4,4'-R'-2,2'-bipyridine)][CF3SO3], where R = CH3, CHO or CH2OH and R' = H, CH3, CH2OH, or dibiotin ester. The complexes (Ru 1-7) displayed high bioactivity, as shown by low IC50 concentrations against CRC cells, namely, RKO and SW480. Four of the most promising ruthenium complexes (Ru 2, 5-7) were phenotypically characterized and were shown to inhibit cell viability by decreasing cell proliferation, inducing cell cycle arrest, and increasing apoptosis. These findings were in accordance with the inhibition of MEK/ERK and PI3K/AKT signaling pathways. Ruthenium complexes also led to a decrease in cellular clonogenic ability and cell migration, which was associated with the disruption of F-actin cytoskeleton integrity. Here, we demonstrated that ruthenium complexes, especially Ru7, have a high anticancer effect against CRC cells and are promising drugs to be used as a new therapeutical strategy for CRC treatment.

| S-EPMC9228117 | biostudies-literature

New Ruthenium-Cyclopentadienyl Complexes Affect Colorectal Cancer Hallmarks Showing High Therapeutic Potential.

Project description:Colorectal cancer (CRC) is among the most deadly cancers worldwide. Current therapeutic strategies have low success rates and several side effects. This relevant clinical problem requires the discovery of new and more effective therapeutic alternatives. Ruthenium drugs have arisen as one of the most promising metallodrugs, due to their high selectivity to cancer cells. In this work we studied, for the first time, the anticancer properties and mechanisms of action of four lead Ru-cyclopentadienyl compounds, namely PMC79, PMC78, LCR134 and LCR220, in two CRC-derived cell lines (SW480 and RKO). Biological assays were performed on these CRC cell lines to evaluate cellular distribution, colony formation, cell cycle, proliferation, apoptosis, and motility, as well as cytoskeleton and mitochondrial alterations. Our results show that all the compounds displayed high bioactivity and selectivity, as shown by low half-maximal inhibitory concentrations (IC50) against CRC cells. We observed that all the Ru compounds have different intracellular distributions. In addition, they inhibit to a high extent the proliferation of CRC cells by decreasing clonogenic ability and inducing cell cycle arrest. PMC79, LCR134, and LCR220 also induce apoptosis, increase the levels of reactive oxygen species, lead to mitochondrial dysfunction, induce actin cytoskeleton alterations, and inhibit cellular motility. A proteomic study revealed that these compounds cause modifications in several cellular proteins associated with the phenotypic alterations observed. Overall, we demonstrate that Ru compounds, especially PMC79 and LCR220, display promising anticancer activity in CRC cells with a high potential to be used as new metallodrugs for CRC therapy.

| S-EPMC10302444 | biostudies-literature

An Unprecedented Family of Luminescent Iridium(III) Complexes Bearing a Six-Membered Chelated Tridentate C^N^C Ligand.

Project description:A new family consisting of three luminescent neutral Ir(III) complexes with the unprecedented [Ir(C^N^C)(N^N)Cl] architecture, where C^N^C is a bis(six-membered) chelating tridentate tripod ligand derived from 2-benzhydrylpyridine (bnpy) and N^N is 4,4'-di-tert-butyl-2,2'-bipyridine (dtBubpy), is reported. X-ray crystallography reveals an unexpected and unusual double C-H bond activation of the two distal nonconjugated phenyl rings of the bnpy coupled with a very short Ir-Cl bond trans to the pyridine of the bnpy ligand. Depending on the substitution on the bnpy ligand, phosphorescence, ranging from yellow to red, is observed in dichloromethane solution. A combined study using density functional theory (DFT) and time-dependent DFT (TD-DFT) corroborates the mixed charge-transfer nature of the related excited states.

| S-EPMC5417592 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data