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1.
Molecules ; 25(10)2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32429279

RESUMO

Ruthenium-based complexes have received much interest as potential metallodrugs. In this work, four RuII complexes bearing a dicarbollide moiety, a carbonyl ligand, and a phenanthroline-based ligand were synthesized and characterized, including single crystal diffraction analysis of compounds 2, 4, and 5 and an observed side product SP1. Complexes 2-5 are air and moisture stable under ambient conditions. They show excellent solubility in organic solvents, but low solubility in water.

2.
Dalton Trans ; 49(15): 4817-4823, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32215416

RESUMO

A one-dimensional {[Zn(L)(DMF)2]}n (1) and a three-dimensional {[Cd(L)(DMF)]·DMF}n (2) coordination polymer based on the novel anthracene derivative H2L (H2L = 4,4'-(9,10-anthracenediyl)dicinnamic acid) were obtained by solvothermal synthesis and charaterised by single-crystal and powder X-ray diffraction, thermogravimetry, and infrared spectroscopy. The anthracene derivative H2L and coordination polymers 1 and 2 were used to modify a glassy carbon electrode and as such served as an active material for detection of H2O2. Cyclic voltammograms in the potential range from 0 to -0.5 V revealed concentration-dependent cathodic current in all three cases with a lower detection limit of 200 µM. The electrode modified with compound 2 showed the best performance towards hydrogen peroxide detection. The results suggest that the development of electrodes modified with inorganic polymers based on highly conjugated ligands can serve as potential electrocatalytic materials.

3.
Sci Rep ; 10(1): 4827, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32179835

RESUMO

Owing to the involvement of cyclooxygenase-2 (COX-2) in carcinogenesis, COX-2-selective inhibitors are increasingly studied for their potential cytotoxic properties. Moreover, the incorporation of carboranes in structures of established anti-inflammatory drugs can improve the potency and metabolic stability of the inhibitors. Herein, we report the synthesis of carborane-containing derivatives of rofecoxib that display remarkable cytotoxic or cytostatic activity in the micromolar range with excellent selectivity for melanoma and colon cancer cell lines over normal cells. Furthermore, it was shown that the carborane-modified derivatives of rofecoxib showed different modes of action that were dependent on the cell type.

4.
J Inorg Biochem ; 203: 110903, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31683124

RESUMO

Three water-soluble tris-heteroleptic ruthenium(II) polypyridyl complexes [Ru(bpy)(phen)(bpg)]2+ (1), [Ru(bpy)(dppz)(bpg)]2+ (2), and [Ru(phen)(dppz)(bpg)]2+ (3) (where bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, dppz = dipyrido[3,2-a:2',3'-c] phenazine, bpg = 4b,5,7,7a-tetrahydro-4b,7a-epiminomethanoimino-6H-imidazo[4,5-f] [1,10] phenanthroline-6,13-dione) have been synthesized and characterized. Molecular structures of complexes 1 and 3 are confirmed by single crystal X-ray structure determination. Interaction of complexes 1-3 with DNA is explored by various spectroscopic techniques. The complexes 1-3 show solvent dependent photophysical properties. Complexes 2 and 3 show extensive "molecular light switch" effect for DNA. The complexes 1-3 are low toxic towards HeLa (human cervical cancer) and HL-60 (human promyelocytic leukemia) cell lines. Further, the cellular uptake of complexes 2 and 3 by cells shows that complexes mainly localised on the nucleus of the cells.

5.
Dalton Trans ; 49(1): 57-69, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31808482

RESUMO

Introduction of a bis(isopropylidene)-protected galactopyranosyl moiety in s-triazine-based boron-rich carboxylic acids and amines results in soluble and suitable coupling partners for tumour-selective biomolecules with applications as selective agents for boron neutron capture therapy (BNCT). Bearing either a carboxylic acid or primary amine as a functional group, these compounds are highly versatile and thus largely extend the possible coupling strategies with suitable biomolecules. Modification of the gastrin-releasing peptide receptor (GRPR) selective agonist [d-Phe6, ß-Ala11, Ala13, Nle14]Bn(6-14) with the carboxylic acid derivative yielded a bioconjugate with an optimal receptor activation and internalisation profile. This demonstrates the great potential of this approach for the development of novel boron delivery agents.

6.
Molecules ; 24(18)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509949

RESUMO

The amount of boron accumulated in tumor tissue plays an important role regarding the success of the boron neutron capture therapy (BNCT). In this article, we report a modular system, combining readily available starting materials, like glycine, 1,3,5-triazine and the well-known 9-mercapto-1,7-dicarba-closo-dodecaborane(12), as well as α-d-galactopyranose for increased hydrophilicity, with a novel boron-rich tris-meta-carboranyl thiol.


Assuntos
Terapia por Captura de Nêutron de Boro , Boro/farmacologia , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Boro/química , Compostos de Boro/síntese química , Compostos de Boro/química , Compostos de Boro/farmacologia , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Ésteres/química , Glicina/química , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Estrutura Molecular , Neoplasias/patologia , Compostos de Sulfidrila/química , Compostos de Sulfidrila/farmacologia , Triazinas/química , Triazinas/farmacologia
7.
ACS Omega ; 4(5): 8824-8833, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31459970

RESUMO

Ketoprofen is a widely used nonsteroidal anti-inflammatory drug (NSAID) that also exhibits cytotoxic activity against various cancers. This makes ketoprofen an attractive structural lead for the development of new NSAIDs and cytotoxic agents. Recently, the incorporation of carboranes as phenyl mimetics in structures of established drugs has emerged as an attractive strategy in drug design. Herein, we report the synthesis and evaluation of four novel carborane-containing derivatives of ketoprofen, two of which are prodrug esters with an nitric oxide-releasing moiety. One of these prodrug esters exhibited high cytostatic activity against melanoma and colon cancer cell lines. The most pronounced activity was found in cell lines that are sensitive to oxidative stress, which was apparently induced by the ketoprofen analogue.

8.
Dalton Trans ; 48(29): 10834-10844, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31246208

RESUMO

Based on a modular combination of s-triazine, the well-known 9-mercapto-1,7-dicarba-closo-dodecaborane(12) and commercially available carboxylic acids, namely thioglycolic acid, glycine, and Nα-Boc-l-lysine, several carboxylic acid derivatives were synthesised and fully characterised. The thioglycolic acid derivative was introduced into a peptide hormone by solid phase peptide synthesis. High activity and selective internalisation into peptide receptor-expressing cells was observed. With a very high boron content of twenty boron atoms, these derivatives are interesting as selective Boron Neutron Capture Therapy (BNCT) agents.

9.
Nanoscale ; 11(27): 13161, 2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31243404

RESUMO

Correction for 'Laser printing of optically resonant hollow crystalline carbon nanostructures from 1D and 2D metal-organic frameworks' by Leila R. Mingabudinova et al., Nanoscale, 2019, 11, 10155-10159.

10.
Nanoscale ; 11(21): 10155-10159, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31038502

RESUMO

Using a hybrid approach involving a slow diffusion method to synthesize 1D and 2D MOFs followed by their treatment with femtosecond infrared laser radiation, we generated 100-600 nm well-defined hollow spheres and hemispheres of graphite. This ultra-fast technique extends the library of shapes of crystalline MOF derivatives appropriate for all-dielectric nanophotonics.

11.
Chemistry ; 25(49): 11456-11465, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31074568

RESUMO

Deboronation of a carborane-substituted diphosphetane 2 in toluene yielded the first nido-carboranyldiphosphetane 1. The P-P bond in 1 can be broken via dismutation reactions with diaryl dichalcogenides yielding nido-carboranyl bis-phosphanes that were not accessible via established synthetic protocols. Additionally, transition metal complexes of 1 could be isolated including one coordination polymer. Notably, when the deboronation of 2 is carried out in ethanol, unprecedented nido-carborane-substituted secondary bis-phosphane monoxides (3, 4) are obtained. These compounds are interesting starting materials for further reactivity studies due to their P-H bonds. Experimental findings are supported by DFT calculations including the calculation of reaction mechanisms and NMR spectroscopic parameters.

12.
ChemMedChem ; 14(3): 315-321, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30602073

RESUMO

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common way of treating inflammatory disorders. Their widespread use helped reveal their other modes of action as pharmaceuticals, such as a profound effect on various cancers. Celecoxib has proven to be a very prominent member of this group with cytostatic activities. On the other hand, the highly dynamic field of drug design is constantly searching for new ways of modifying known structures to obtain more powerful and less harmful drugs. A very interesting development is the implementation of carboranes in pharmacologically active structures, mostly as phenyl mimetics. Herein we report the synthesis of three carborane-containing derivatives of the COX-2-selective NSAID celecoxib. The new compounds proved to have promising cytostatic potential against various melanoma and colorectal adenocarcinoma cell lines. Inhibited proliferation accompanied by caspase-independent apoptotic cell death was found to be the main cause of decreased cell viability upon treatment with the most efficient celecoxib analogue, 3 b (4-[5-(1,7-dicarba-closo-dodecaboranyl)-3-trifluoromethyl-1H-pyrazol-1-yl]-1-methylsulfonylbenzene).


Assuntos
Antineoplásicos/farmacologia , Celecoxib/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Citostáticos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Celecoxib/síntese química , Celecoxib/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Citostáticos/síntese química , Citostáticos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade
13.
ChemMedChem ; 14(2): 255-261, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30471171

RESUMO

5-Lipoxygenase converts arachidonic acid into leukotrienes, which are involved in inflammation and angiogenesis. The introduction of carboranes can improve the pharmacokinetic behavior of metabolically less stable pharmaceutics. Herein we report the syntheses of several carborane-based inhibitors of the 5-lipoxygenase pathway. The isosteric replacement of phenyl rings by carboranes leads to improved cytotoxicity toward several melanoma and colon cancer cell lines. For the colon cancer cell line HCT116, the co-inhibition of heat shock protein 90 was observed.


Assuntos
Boranos/química , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Inibidores de Lipoxigenase/química , Inibidores de Lipoxigenase/farmacologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Desenho de Fármacos , Células HCT116 , Humanos
14.
Chempluschem ; 84(3): 307-313, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31950765

RESUMO

A luminescent zinc-based metal-organic framework (MOF; 1) was synthesized from a highly conjugated tridentate ligand, 1,3,5-tris[(1E)-2'-(4''-benzoic acid)vinyl]benzene. X-ray single crystal analysis reveals the organization of 1 in a three-dimensional porous framework. Thermogravimetric analysis shows that 1 has a good thermal stability, and resists decomposition up to 420 °C. The removal of the solvent molecules from the cavities leads to a temporary loss of crystallinity, which can be regained by heating the MOF in diethylformamide, the solvent used for the synthesis, as shown by powder X-ray diffraction. In addition, 1 shows luminescent features influenced by the chemical environment, making it suitable as optical sensor. Detection of methanol with a turn-on effect was possible in low concentration in mixtures with water (50 µL/3 mL and 10 µL/3 mL) and as vapor.

15.
Acta Crystallogr E Crystallogr Commun ; 74(Pt 9): 1336-1338, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30225128

RESUMO

The title pseudo-polymorph of 3-(tri-phenyl-phospho-ranyl-idene)-2,5-di-hydro-furan-2,5-dione crystallizes with a tetra-hydro-furan solvent mol-ecule, viz. C22H17O3P·C4H8O. The succinic anhydride ring is approximately planar (r.m.s. deviation = 0.032 Å). The tetra-hydro-furan mol-ecule is disordered over two orientations about a pseudo-twofold axis with refined occupancy ratio 0.718 (4):0.282 (4). In the crystal, C-H⋯O hydrogen bonds link mol-ecules of the di-hydro-furan-2,5-dione derivative into chains parallel to the b axis and arranged into layers stacked along [100] alternating with hydrogen-bonded tetra-hydro-furan layers.

16.
Dalton Trans ; 47(41): 14515-14520, 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30234867

RESUMO

The tridentate phosphine ligand 1,3,5-tris[(E)-(4-phospholano-2,6-diethyl)styryl]benzene (1) reacts with [AuCl(tht)] (tht = tetrahydrothiophene) independent of the stoichiometry employed with selective formation of a two-dimensional coordination polymer (ratio 1 : 1) with the gold(i) cations in a trigonal-planar [3 + 1] coordination geometry. Each of the three coordinating phosphine units originates from another ligand, thus forming a polymeric structure.

17.
Inorg Chem ; 57(6): 3297-3304, 2018 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-29509417

RESUMO

1,3,5-Triphospha-1,4-pentadiene-2,4-diamine reacts with [M(CO)4L] (M = Mo, L = nbd (norbornadiene); M = W, L = 2 CH3CN) to give the chelate complexes [M(CO)4(PMes{C(NHCy)PMes}2-κ P1 ,P3)]. In contrast, an unusual intramolecular rearrangement occurred with [Cu(CH3CN)4]PF6 leading to the dimeric copper(I) complex [Cu(CNCy){PHMesPMesC(NHCy)PMes-κ P1 ,P3}]2(PF6)2. The mechanism of the rearrangement was supported by quantum-mechanical calculations. The transition-metal complexes were characterized by multinuclear NMR spectroscopy, mass spectrometry, infrared spectroscopy, and X-ray crystallography.

18.
Chemistry ; 24(23): 6208-6216, 2018 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-29441623

RESUMO

Carborane-substituted 1,2-diphosphetanes (Ia,b) react with elemental lithium in THF with cleavage of the P-P bond to give a deep red solution from which, in the case of Ia, red crystals of a lithiated intermediate, [{1-Li(THF)PtBu-6-PtBu-4,1,6-closo-Li(THF)C2 B10 H10 }{Li(THF)3 }]2 ⋅2 THF (2 a), are obtained. The compound is dimeric, C2 -symmetric and contains six lithium and four phosphorus atoms. Two lithium atoms cap the six-membered C2 B4 faces, resulting in two 13-vertex closo-clusters (according to Wade's rules) with docosahedral geometry. The addition of methyl iodide resulted in the formation of zwitterionic bis-phosphonium-nido-carborates 7,10-bis(tert-butyldimethylphosphonium)dodecahydro-7,10-dicarba-nido-dodecaborate(2-) (1 a) and 7,10-bis(N,N-diisopropylaminodimethylphosphonium)dodecahydro-7,10-dicarba-nido-dodecaborate(2-) (1 b) in moderate to good yields. Compounds 1 a and 1 b exhibit short Ccluster -P bonds and large Ccluster ⋅⋅⋅Ccluster distances in the solid state. Further insight into the ring opening and reduction potential of the alkyl halide was obtained from methylation reactions of different 1,2-bis-phosphinocarboranes. The reaction of rac-/meso-1,2-bis(tert-butylmethylphosphino)-1,2-dicarba-closo-dodecaborane(12) (3 a) with two equivalents of methyl iodide also resulted in the formation of 1 a (as shown by NMR spectroscopy), whereas the reaction of 1,2-bis(diphenylphosphino)-1,2-dicarba-closo-dodecaborane(12) with methyl triflate afforded the phosphonium salt 1-methyl-diphenylphosphonium-2-diphenylphosphino-1,2-dicarba-closo-dodecaborane(12) triflate (4) without reduction of the cluster.

19.
Dalton Trans ; 46(36): 12067-12080, 2017 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-28799598

RESUMO

Three [(η6-arene)RuC2B9H11] complexes (arene = p-cymene (2), biphenyl (3) and 1-Me-4-COOEt-C6H4 (4)) were synthesised according to modified literature procedures and fully characterised. 2-4 were found to be moderately active against two types of tumour cell lines (HCT116 and MCF7), with IC50 values in the low micromolar range. However, viability of normal, healthy cells (MRC-5 cell line, MLEC and mouse macrophages) was not affected by treatment with 2-4, indicating high selectivity of the metallacarborane complexes towards tumour cell lines, compared to the unselective antitumour agent cisplatin and other potential RuII drugs. Moreover, flow cytometric analysis suggested that 4 induces cell death via a caspase-dependent apoptotic mechanism. DFT calculations of the frontier molecular orbitals showed that the HOMO-LUMO gap in 2-4 is smaller than in the corresponding cyclopentadienyl complexes 2-Cp-4-Cp (e.g. 5.47 (2) vs. 6.31 eV (2-Cp)). In order to assess the stability of 2-4, particularly the ruthenium-dicarbollide bond, energy decomposition analysis (EDA) of 2-4, together with the respective cyclopentadienyl analogues 2-Cp-4-Cp, was performed. EDA suggests that the ruthenium(ii)-dicarbollide bond in the three complexes is mostly ionic and far stronger than the ruthenium(ii)-arene bond.


Assuntos
Antineoplásicos/química , Complexos de Coordenação/química , Rutênio/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Boranos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Cristalografia por Raios X , Células HCT116 , Humanos , Células MCF-7 , Microscopia de Fluorescência , Conformação Molecular , Teoria Quântica , Termodinâmica
20.
ChemMedChem ; 12(13): 1081-1086, 2017 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-28569429

RESUMO

The progression of cancer is accelerated by increased proliferation, angiogenesis, and inflammation. These processes are mediated by leukotrienes. Several cancer cell lines overexpress 5-lipoxygenase, an enzyme that converts arachidonic acid into leukotrienes. An early inhibitor of the 5-lipoxygenase pathway is Rev-5901, which, however, lacks in in vivo efficacy, as it is rapidly metabolized. We investigated the introduction of carboranes as highly hydrophobic and metabolically stable pharmacophores into lipoxygenase inhibitors. Carboranes are icosahedral boron clusters that are remarkably stable and used to increase the metabolic stability of unstable pharmaceutics without changing their biological activity. By introduction of meta-carborane into Rev-5901, the first carborane-based inhibitor of the 5-lipoxygenase pathway was obtained. We report the synthesis and inhibitory and cytotoxic behavior of these compounds toward several melanoma and colon cancer cell lines and their related anticancer mechanisms.


Assuntos
Antineoplásicos/farmacologia , Araquidonato 5-Lipoxigenase/metabolismo , Compostos de Boro/farmacologia , Inibidores de Lipoxigenase/farmacologia , Quinolinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Compostos de Boro/síntese química , Compostos de Boro/toxicidade , Linhagem Celular Tumoral , Humanos , Inibidores de Lipoxigenase/síntese química , Inibidores de Lipoxigenase/toxicidade , Simulação de Acoplamento Molecular , Óxido Nítrico/metabolismo , Quinolinas/síntese química , Quinolinas/química , Quinolinas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
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