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1.
Molecules ; 25(10)2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32455529

RESUMO

The histone deacetylase (HDAC) enzymes have emerged as an important class of molecular targets in cancer therapy, with five inhibitors in clinical use. Recently, it has been shown that a lack of selectivity between the 11 Zn-dependent HDAC isoforms may lead to unwanted side-effects. In this paper, we show that piano stool Ru complexes can act as HDAC inhibitors, and variation in the capping arene leads to differences in HDAC isoform selectivity.

2.
Org Biomol Chem ; 15(43): 9186-9190, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29072756

RESUMO

A series of potent histone deacetylase inhibitors is presented that incorporate alkyl or perfluorinated alkyl chains. Several new compounds show greater in vitro antiproliferative activity than the clinically approved inhibitor, SAHA. Furthermore, the new compounds show up to 5-fold greater activity against cancer cells than healthy cells. This selectivity is in contrast to SAHA, which is more active against the healthy cell line than the cancer cell line tested. Finally, we report an increase in activity for SAHA under mild hyperthermia, indicating that it could be an interesting candidate to use in combination with thermal therapy.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Halogenação , Inibidores de Histona Desacetilases/química , Inibidores de Histona Desacetilases/farmacologia , Linhagem Celular Tumoral , Histona Desacetilases/química , Histona Desacetilases/metabolismo , Humanos , Modelos Moleculares , Conformação Proteica , Proteínas Repressoras/química , Proteínas Repressoras/metabolismo
3.
Chem Commun (Camb) ; 53(71): 9858-9861, 2017 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-28825074

RESUMO

A novel trifluoromethylation of arenes is presented, which proceeds under mild reaction conditions and has the potential for late-stage functionalisation of pharmaceuticals and agrochemicals. The new reaction allows for the regioselective conversion of nitroarenes into 1,2-trifluoromethylated nitroarenes, via a C-H activation pathway. Furthermore, a substitution of nitroarenes to trifluoromethyl arenes is also presented.

4.
Fam Pract ; 33(5): 523-8, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27418587

RESUMO

BACKGROUND: Type II diabetes continues to be a major health problem in USA, particularly in minority populations. The Diabetes Equity Project (DEP), a clinic-based diabetes self-management and education program led by community health workers (CHWs), was designed to reduce observed disparities in diabetes care and outcomes in medically underserved, predominantly Hispanic communities. OBJECTIVE: The purpose of this study was to evaluate the impact of the DEP on patients' clinical outcomes, diabetes knowledge, self-management skills, and quality of life. METHODS: The DEP was implemented in five community clinics from 2009 to 2013 and 885 patients completed at least two visits with the CHW. Student's paired t-tests were used to compare baseline clinical indicators with indicators obtained from patients' last recorded visit with the CHW and to assess differences in diabetes knowledge, perceived competence in managing diabetes, and quality of life. A mixed-effects model for repeated measures was used to examine the effect of DEP visits on blood glucose (HbA1c), controlling for patient demographics, clinic and enrolment date. RESULTS: DEP patients experienced significant (P < 0.0001) improvements in HbA1c control, blood pressure, diabetes knowledge, perceived competence in managing diabetes, and quality of life. Mean HbA1c for all DEP patients decreased from 8.3% to 7.4%. CONCLUSION: Given the increasing prevalence of diabetes in USA and documented disparities in diabetes care and outcomes for minorities, particularly Hispanic patients, new models of care such as the DEP are needed to expand access to and improve the delivery of diabetes care and help patients achieve improved outcomes.


Assuntos
Agentes Comunitários de Saúde , Assistência à Saúde/normas , Diabetes Mellitus Tipo 2/terapia , Conhecimentos, Atitudes e Prática em Saúde , Adulto , Feminino , Hemoglobina A Glicada/análise , Hispano-Americanos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Autocuidado/métodos , Texas/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Populações Vulneráveis
5.
Dalton Trans ; 45(32): 12807-13, 2016 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-27468432

RESUMO

For the first time, a series of 25 pseudo-octahedral pyridylphosphinate metal complexes (Ru, Os, Rh, Ir) has been synthesised and assessed in biological systems. Each metal complex incorporates a pyridylphosphinate ligand, a monodentate halide and a capping η(6)-bound aromatic ligand. Solid- and solution-state analyses of two complexes reveal a structural preference for one of a possible two diastereomers. The metal chlorides hydrolyse rapidly in D2O to form a 1 : 1 equilibrium ratio between the aqua and chloride adducts. The pKa of the aqua adduct depends upon the pyridyl substituent and the metal but has little dependence upon the phosphinate R' group. Toxicity was measured in vitro against non-small cell lung carcinoma H460 cells, with the most potent complexes reporting IC50 values around 50 µM. Binding studies with selected amino acids and nucleobases provide a rationale for the variation in toxicity observed within the series. Finally, an investigation into the ability of the chelating amino acid l-His to displace the phosphinate O-metal bond shows the potential for phosphinate complexes to act as prodrugs that can be activated in the intracellular environment.


Assuntos
Complexos de Coordenação , Metais Pesados , Compostos Organofosforados , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Histidina/química , Histidina/farmacologia , Humanos , Metais Pesados/química , Metais Pesados/farmacologia , Estrutura Molecular , Compostos Organofosforados/química , Compostos Organofosforados/farmacologia , Pró-Fármacos/química , Pró-Fármacos/farmacologia
6.
Chem Commun (Camb) ; 51(14): 2786-9, 2015 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-25300517

RESUMO

We present nucleophilic aromatic substitution of unsubstituted aryl chlorides via a mechanism that is catalytic in [CpRu(p-cymene)]PF6 and involves a Ru(η(6)-arylchloride) intermediate. From the spectroscopic evidence we infer that arene exchange is the rate limiting step in this process and develop several new Ru(ii) complexes that lower the activation barrier to arene exchange.

7.
Dalton Trans ; 44(11): 4791-803, 2015 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-25341077

RESUMO

The development of the brightest luminescent europium(iii) complexes is traced, including analysis of the C3-symmetric core complex based on a functionalized triazacyclononane and identification of the most suitable strongly absorbing chromophore. Strategies for the synthesis of the complexes, including enantiopure analogues, are outlined and opportunities for applications in time-resolved microscopy and spectral imaging emphasised. Practicable examples are introduced, including selective organelle staining for cellular optical imaging at 65 nm resolution and the development of new bioassays using time-resolved FRET methods.


Assuntos
Bioensaio/métodos , Corantes/síntese química , Európio/química , Imagem Óptica/métodos , Compostos Organometálicos/síntese química , Animais , Técnicas de Química Sintética , Corantes/química , Corantes/metabolismo , Humanos , Compostos Organometálicos/química , Compostos Organometálicos/metabolismo
8.
Chemistry ; 20(28): 8636-46, 2014 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-24938657

RESUMO

A series of europium and terbium complexes based on a functionalized triazacyclononane carboxylate or phosphinate macrocyclic ligand is described. The influence of the anionic group, that is, carboxylate, methylphosphinate, or phenylphosphinate, on the photophysical properties was studied and rationalized on the basis of DFT calculated structures. The nature, number, and position of electron-donating or electron-withdrawing aryl substituents were varied systematically within the same phenylethynyl scaffold in order to optimize the brightness of the corresponding europium complexes and investigate their two-photon absorption properties. Finally, the europium complexes were examined in cell-imaging applications, and selected terbium complexes were studied as potential oxygen sensors.


Assuntos
Alquinos/química , Compostos Aza/química , Európio/química , Compostos Organometálicos/química , Piperidinas/química , Térbio/química , Ligantes , Estrutura Molecular
9.
Chemistry ; 19(29): 9511-7, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23744790

RESUMO

A series of five europium(III) complexes has been prepared from heptadentate N5O2 ligands that possess a brightness of more than 10 mM(-1) cm(-1) in water, following excitation over the range λ=330-355 nm. Binding of several oxy anions has been assessed by emission spectral titrimetric analysis, with the binding of simple carboxylates, lactate and citrate involving a common ligation mode following displacement of the coordinated water. Selectivity for bicarbonate allows the rapid determination of this anion in human serum, with K(d)=37 mM (295 K). The complexes are internalised quickly into mammalian cells and exhibit a mitochondrial localisation at early time points, migrating after a few hours to reveal a predominant lysosomal distribution. Herein, we report the synthesis and complexation behaviour of strongly emissive europium (III) complexes that bind oxy-anions in aqueous media with an affinity and selectivity profile that is distinctively different from previously studied systems.


Assuntos
Ânions/química , Compostos Aza/química , Bicarbonatos/análise , Bicarbonatos/química , Ácido Cítrico/química , Európio/análise , Európio/química , Piperidinas/química , Soro/química , Humanos , Ligantes , Luminescência , Soro/metabolismo
10.
Chem Commun (Camb) ; 49(16): 1600-2, 2013 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-23336102

RESUMO

The synthesis, structure and photophysical properties of a series of highly emissive europium complexes is reported. Certain complexes enter mammalian cells by macropinocytosis and stain the mitochondria selectively, allowing observation of the Eu emission in cellulo by time-gated spectral imaging.


Assuntos
Európio/análise , Európio/química , Mitocôndrias/química , Amilorida/farmacologia , Androstadienos/farmacologia , Animais , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Moleculares , Estrutura Molecular , Células NIH 3T3 , Compostos Organometálicos/análise , Compostos Organometálicos/antagonistas & inibidores , Compostos Organometálicos/química , Temperatura , Wortmanina
11.
Chem Commun (Camb) ; 48(95): 11626-8, 2012 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-23097018

RESUMO

Zirconocene dichloride (Cp(2)ZrCl(2)) has been shown to be an effective catalyst for the transamidation of primary amides with amines in cyclohexane at 80 °C in 5-24 hours. For favourable substrates, the reaction can be performed at temperatures as low as 30 °C.


Assuntos
Amidas/química , Aminas/química , Compostos Organometálicos/química , Zircônio/química , Carbamatos/química , Catálise , Cicloexanos/química , Temperatura
13.
Inorg Chem ; 51(15): 8042-56, 2012 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-22809198

RESUMO

Nonadentate ligands based on triazacyclononane incorporating pyridyl-2-phosphinate groups form an isostructural series of complexes with Ln ions in the solid state and in solution. The Ln ion is effectively shielded from the solvent environment. Crystal structures reveal a rigid C(3)-symmetric tricapped trigonal-prismatic coordination geometry that is maintained in solution for the methyl and phenylphosphinate series, as shown by multinuclear NMR analysis. Variable-temperature measurements of the field dependence of the water proton relaxivity in gadolinium complexes indicate that these systems exclude solvent from the primary coordination environment and minimize the second sphere of solvation. The electronic relaxation time for the gadolinium methylphosphinate complex has been estimated to be 550 (±150) ps by EPR and NMR methods, compared to values of around 0.30-0.05 ps for the terbium-ytterbium series, deduced by analyzing the field dependence (4.7-16.5 T) of the (31)P NMR longitudinal relaxation times. Values are compared with analogous azacarboxylate ligand complexes, supporting a key role for donor atom polarizability in determining the electronic relaxation. Spectral emission behavior in solution of samarium, europium, terbium, and dysprosium complexes is compared, and the resolved RRR-Λ and SSS-Δ complexes show strong circularly polarized luminescence. The molecular quadratic hyperpolarizability 〈ß(HLS)〉 has been measured in solution using hyper-Raleigh light-scattering methods, for the whole series of lanthanide complexes of one ligand. The values of 〈ß(HLS)〉 reach a maximum around the center of the series and are not simply dependent on the number of f electrons, suggesting a dominant contribution from the octupolar rather than the dipolar term.

14.
Fam Community Health ; 35(2): 161-71, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22367263

RESUMO

Disparities in prevalence of type 2 diabetes and complications in underserved populations have been linked to poor quality of care including lack of access to diabetes management programs. Interventions utilizing community health workers (CHWs) to assist with diabetes management have demonstrated improvements in patient outcomes. Use of CHWs may be an effective model for providing care coordination and reducing disparities, but there is limited knowledge on how to implement this model on a large scale. This article describes how an integrated health care system implemented a CHW-led diabetes self-management education program targeting Hispanic patients and reports lessons learned from the first 18 months of operation.


Assuntos
Agentes Comunitários de Saúde , Diabetes Mellitus/prevenção & controle , Implementação de Plano de Saúde , Educação de Pacientes como Assunto , Autocuidado/métodos , Agentes Comunitários de Saúde/educação , Prestação Integrada de Cuidados de Saúde/organização & administração , Humanos , Liderança , Desenvolvimento de Programas
15.
Chem Commun (Camb) ; 47(45): 12289-91, 2011 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-22010133

RESUMO

Lanthanide complexes of a pyridylphenylphosphinate ligand based on triazacyclononane form an isostructural series. The C(3)-symmetric Δ and Λ complexes of Eu and Tb are strongly emissive and can be resolved by chiral HPLC; the absolute configuration of each complex has been assigned using CD and CPL measurements.

16.
Dalton Trans ; 39(41): 9897-903, 2010 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-20848045

RESUMO

Two di-aqua Eu(iii) complexes of heptadentate ligands are reported that show differing reactivity profiles towards various anions; a cationic complex with two azaxanthone moieties exhibits pronounced selectivity towards bicarbonate with an affinity constant, logK = 2.65 (295 K, 0.1 M NaCl).

17.
Chem Commun (Camb) ; 46(14): 2391-3, 2010 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-20309461

RESUMO

The emission intensity of a monocationic Tb or Eu(III) complex of a bis(1-azaxanthone) ligand is enhanced in the presence of serum albumin; the lanthanide complex stains dividing cells, allowing visualisation of mitotic chromosomes.


Assuntos
Complexos de Coordenação/química , DNA/química , Térbio/química , Európio/química , Células HeLa , Humanos , Ligantes , Luminescência , Microscopia de Fluorescência
18.
Curr Opin Chem Biol ; 14(2): 238-46, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19884038

RESUMO

Useful probes of the intracellular environment are required for a wide range of bioactive species including metal ions, oxyanions and pH. These probes need to be targeted to specific organelles (mitochondria, nucleus and lysosomes) in order to allow direct observation of the changes in these regions. Critical probe design features for luminescent lanthanide complexes are defined, together with a review of published sub-cellular localisation profiles. Cell uptake by macropinocytosis has been demonstrated for a wide range of probes and the importance of minimising perturbation of cellular homeostasis emphasised, so that cell viability, proliferation and membrane permeability are not compromised.


Assuntos
Técnicas Citológicas/métodos , Elementos da Série dos Lantanídeos/análise , Elementos da Série dos Lantanídeos/metabolismo , Animais , Transporte Biológico , Humanos , Luminescência
19.
J Health Care Poor Underserved ; 19(4): 1076-95, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19029738

RESUMO

The feasibility of a newly designed Community Diabetes Education (CoDE) intervention was evaluated in preparation for the development of a pilot study of this program. A comparison between CoDE and similar culturally appropriate diabetes management programs developed specifically for Hispanic Americans demonstrates its unique features. Patient insurance status, duration of the intervention, delivery in individual and/or group settings, the characteristics of the diabetes educator(s), the other professional resources involved in these interventions, the associated costs, and the reported health outcomes were used in the comparison. The significant improvement in hemoglobin A1c observed in patients who completed one year of CoDE suggests that a community health worker can serve as the primary patient educator in the absence of more highly educated personnel required by American Diabetes Association-certified diabetes education programs. This low-cost model can be reproduced de novo in community health centers or inserted into existing diabetes management interventions.


Assuntos
Agentes Comunitários de Saúde/organização & administração , Características Culturais , Diabetes Mellitus/etnologia , Diabetes Mellitus/terapia , Educação em Saúde/organização & administração , Hispano-Americanos , Adolescente , Adulto , Fatores Etários , Pesos e Medidas Corporais , Feminino , Hemoglobina A Glicada/análise , Comportamentos Relacionados com a Saúde , Humanos , Cobertura do Seguro/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pobreza , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
20.
Proc (Bayl Univ Med Cent) ; 20(2): 111-7, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17431443

RESUMO

Low-cost diabetes education programs that target Mexican Americans are essential to reduce the observed health disparities in this population. A culturally appropriate intervention was developed as the centerpiece of the Community Diabetes Education (CoDE) program. This article describes the structure, patient acceptance, and costs of this one-to-one educational model delivered in 7 patient contact hours by a community health worker over 12 months in a community clinic serving the uninsured. A total of 162 patients-predominantly female, Spanish-speaking Mexican American patients with type 2 diabetes of mean duration of 6.5 years-enrolled in the program, and a dropout rate of 22% was observed during the 12-month period. Preliminary analysis indicated that program capacity was 120 patients per month, and the annual direct medical expenditure per CoDE participant was $461. The hemoglobin A(1c) was significantly reduced in patients who participated in the program for 12 months. Sustainable, low-cost, community-based programs like CoDE and long-term patient participation will help reduce the burden of diabetes in the underserved Hispanic population.

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