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1.
J Mater Chem B ; 8(36): 8323-8336, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32793936

RESUMO

Exploiting two-dimensional nanomaterials as photo-based theranostic agents is promising for the highly efficient ablation of deep-tissue-buried tumors. However, they are limited by their poor absorption in the second near-infrared-light (NIR-II) bio-window (1000-1300 nm) and intrinsic nonbiodegradability. Herein, defect-rich sulfur-doped Ni(OH)2 (S-Ni(OH)2) nanosheets decorated with bovine serum albumin (BSA) as a novel theranostic agent is developed, which can accomplish multimodal-imaging-guided photothermal ablation of mouse cancers in the NIR-II bio-window. Sulfur doping extends the absorption spectra of Ni(OH)2 nanosheets from the visible to NIR-II bio-window, affording highly efficient photothermal conversion (58.20% for 1064 nm), entailing it to become an excellent contrast agent for photoacoustic imaging. Further, because of their intrinsic paramagnetic property, they can be applied for magnetic resonance imaging. Owing to the abundant defective sites in S-Ni(OH)2 nanosheets, they exhibit response to the tumor microenvironment, resulting in effective biodegradation and excretion from the body. In vivo toxicity experiments indicated that S-Ni(OH)2-BSA NSs delivered no appreciable toxicity and good biocompatibility. This work provides an avenue for the rational design of effective theranostics agents.


Assuntos
Antineoplásicos/uso terapêutico , Hidróxidos/uso terapêutico , Nanoestruturas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Níquel/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Bovinos , Feminino , Células HeLa , Humanos , Hidróxidos/química , Hidróxidos/farmacocinética , Hidróxidos/efeitos da radiação , Raios Infravermelhos , Camundongos Endogâmicos ICR , Imagem Multimodal , Nanoestruturas/química , Nanoestruturas/efeitos da radiação , Níquel/química , Níquel/farmacocinética , Níquel/efeitos da radiação , Terapia Fototérmica , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética , Soroalbumina Bovina/uso terapêutico , Enxofre/química , Enxofre/farmacocinética , Enxofre/efeitos da radiação , Enxofre/uso terapêutico , Nanomedicina Teranóstica
2.
Phytochemistry ; 72(14-15): 1927-32, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21601897

RESUMO

C9-iridoid glycosides, wallichiisides A-C, and four dimers, wallichiisides D-G, together with 13 known glycosidic compounds, were isolated from whole plants of Eriophyton wallichii Benth. Their structures were elucidated by spectroscopic methods and comparison with literature values. Four of these compounds showed moderate DPPH free radical scavenging activity.


Assuntos
Glicosídeos Iridoides/química , Lamiaceae/química , Extratos Vegetais/química , Dimerização , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Glicosídeos Iridoides/isolamento & purificação , Medicina Tradicional Tibetana , Estrutura Molecular , Plantas Medicinais/química , Tibet
3.
Zhonghua Nan Ke Xue ; 15(3): 207-11, 2009 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-19452690

RESUMO

OBJECTIVE: To investigate the effects of phytoestrogens (daidzein and genistein) on the testosterone production of rat Leydig cells and the possible mechanisms. METHODS: Primary Leydig cells were obtained from 3-month old male SD rats using discontinuous Percoll density gradient centrifugation. The effects of phytoestrogens at various concentrations were evaluated by ELISA, with hCG as the positive control. The mRNA expression of P450 side-chain cleavage enzyme (P450scc) was analyzed by semi-quantitative RT-PCR. RESULTS: Genistein at 0.1 micromol/L obviously promoted the secretion of testosterone and upregulated the mRNA level of P450scc. At a higher concentration of 5 micromol/L, however, both daidzein and genistein significantly inhibited the testosterone production of Leydig cells (P > 0.05). CONCLUSION: Genistein can promote the testosterone production of Leydig cells at a low concentration (0.1 micromol/L), but both daidzein and genistein can inhibit it at a higher concentration ( >5 micromol/L).


Assuntos
Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Fitoestrógenos/farmacologia , Testosterona/biossíntese , Animais , Células Cultivadas , Genisteína/farmacologia , Isoflavonas/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley
4.
Biol Pharm Bull ; 32(3): 389-93, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19252283

RESUMO

Oxidative stress plays an important role in tissue damage associated with many different chronic degenerative diseases, such as cancer and cardiovascular disorders. In our previous study, a novel dipeptide Pro-Arg derived from protamine hydrolysates was found to possess significant antioxidative activity in vitro. In this study, we compared the antioxidant capabilities of purified and synthesized dipeptide (Pro-Arg) and found both of them had very strong hydroxyl-radical scavenging activity in vitro, even at a very low concentration. The protective effect of the dipeptide against oxidative stress was evaluated using H2O2-induced oxidative stress of human diploid fibroblasts MRC-5 cell model. Our results showed the dipeptide attenuated H2O2-induced cellular oxidative damage, and normalized S phase arrest of MRC-5 cells exposed to H2O2. Our findings demonstrate that Pro-Arg can protect against oxidative stress/damage and H2O2-induced human diploid fibroblasts cell death.


Assuntos
Antioxidantes/farmacologia , Dipeptídeos/farmacologia , Fibroblastos/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Protaminas/química , Antioxidantes/isolamento & purificação , Ciclo Celular/efeitos dos fármacos , Dipeptídeos/isolamento & purificação , Diploide , Fibroblastos/citologia , Fibroblastos/metabolismo , Sequestradores de Radicais Livres/isolamento & purificação , Humanos , Hidrólise , Espécies Reativas de Oxigênio/metabolismo
5.
Bioorg Med Chem Lett ; 18(23): 6293-7, 2008 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-18951783

RESUMO

The discovery and initial optimization of a novel anthranilic acid derived class of antibacterial agents has been described in a recent series of papers. This paper describes the discovery of 1-acylindazol-3-ols as a novel bioisostere of an anthranilic acid. The synthesis and structure-activity relationships of the indazol bioisosteres are described herein.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Indazóis/síntese química , Indazóis/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , ortoaminobenzoatos/química , Antibacterianos/química , Técnicas de Química Combinatória , Cristalografia por Raios X , Indazóis/química , Testes de Sensibilidade Microbiana , Conformação Molecular , Estrutura Molecular , Relação Estrutura-Atividade
6.
Antimicrob Agents Chemother ; 52(8): 2806-12, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18519725

RESUMO

QPT-1 was discovered in a compound library by high-throughput screening and triage for substances with whole-cell antibacterial activity. This totally synthetic compound is an unusual barbituric acid derivative whose activity resides in the (-)-enantiomer. QPT-1 had activity against a broad spectrum of pathogenic, antibiotic-resistant bacteria, was nontoxic to eukaryotic cells, and showed oral efficacy in a murine infection model, all before any medicinal chemistry optimization. Biochemical and genetic characterization showed that the QPT-1 targets the beta subunit of bacterial type II topoisomerases via a mechanism of inhibition distinct from the mechanisms of fluoroquinolones and novobiocin. Given these attributes, this compound represents a promising new class of antibacterial agents. The success of this reverse genomics effort demonstrates the utility of exploring strategies that are alternatives to target-based screens in antibacterial drug discovery.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Proteínas de Bactérias/antagonistas & inibidores , Inibidores da Topoisomerase II , Animais , Antibacterianos/química , Antibacterianos/farmacocinética , Área Sob a Curva , Bactérias/enzimologia , Infecções Bacterianas/metabolismo , Infecções Bacterianas/microbiologia , Infecções Bacterianas/prevenção & controle , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Taxa de Depuração Metabólica , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/enzimologia , Estereoisomerismo
7.
Zhongguo Zhong Yao Za Zhi ; 33(22): 2636-9, 2008 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-19216160

RESUMO

OBJECTIVE: To study the chemical constituents of Eriophyton wallichii. METHOD: Compounds were separated and purified by column chromatographic methods, and their structures were elucidated by spectroscopic methods. RESULT: Eight phenylpropanoids were isolated and identified as martynoside (1), leucosceptoside A (2), citrusin B (3), (+)-dehydrodiconiferyl alcohol-4, 9-beta-D-glucopyranoside (4), liriodendrin (5), velutinoside 11[ (6), jionoside B, (7), stachysoside D (8), respectively. CONCLUSION: The eight compounds were firstly isolated from E. wallichii.


Assuntos
Arecaceae/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Fenilpropionatos/química , Fenilpropionatos/isolamento & purificação , Furanos/química , Furanos/isolamento & purificação , Glucosídeos/química , Glucosídeos/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação
8.
Bioorg Med Chem Lett ; 17(10): 2823-7, 2007 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-17368020

RESUMO

In the past few years, a significant effort has been devoted by Pharmacia toward the discovery of novel antibiotics. We have recently described the identification of an anthranilic acid lead 1 and the optimization resulting in the advanced lead 2. In this report, we describe the preparation of several selected amide bioisosteres connecting the A- and the B-rings. The E-alkene provided a rigid analog with equal potency to the corresponding amide. This indicates that the amide is not a recognition element rather acts as an appropriate spatial linker of the two important aryl A and B rings. The work here clearly demonstrates that the amide linker can be replaced with several functionalities without significant deterioration in the MIC activity.


Assuntos
Antibacterianos/farmacologia , ortoaminobenzoatos/química , ortoaminobenzoatos/farmacologia , Antibacterianos/química , Desenho de Fármacos , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
9.
Bioorg Med Chem ; 14(24): 8219-48, 2006 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-17011782

RESUMO

A novel set of azabicyclic aryl amides have been identified as potent and selective agonists of the alpha7 nAChR. A two-pronged approach was taken to improve the potential hERG liability of previously disclosed alpha7 nAChR agonist, PNU-282,987, while maintaining the compound's other desirable pharmacological properties. The first approach involved further exploration of the aryl carboxylic acid fragment of PNU-282,987, while the second approach focused on modification of the azabicyclic amine portion of PNU-282,987. The best compounds from each series are characterized by rapid brain penetration, good oral bioavailability in rat, and demonstrate in vivo efficacy in a rat P50 auditory sensory gating assay. At least one analog from each series (1h, 1o, 2a, 9a, and 18a) shows an improved hERG safety profile over PNU-282,987.


Assuntos
Encéfalo/metabolismo , Desenho de Fármacos , Agonistas Nicotínicos/farmacologia , Receptores Nicotínicos/química , Animais , Bungarotoxinas , Células Cultivadas , Eletrofisiologia , Potenciais Evocados Auditivos/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Ativação do Canal Iônico/efeitos dos fármacos , Estrutura Molecular , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Agonistas Nicotínicos/síntese química , Agonistas Nicotínicos/química , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Sinapses/efeitos dos fármacos , Sinapses/fisiologia , Receptor Nicotínico de Acetilcolina alfa7
10.
Dalton Trans ; (23): 3941-2, 2004 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-15558117

RESUMO

An "arrested" chloride abstraction occurs in the reaction of trans-RuCl(2)(DMeOPrPE)(2) with TlPF(6); the product is a 1-D coordination polymer in which the Tl(I) centers have an unusual octahedral coordination geometry with a stereochemically active 6s(2) lone pair.

11.
J Org Chem ; 67(10): 3317-22, 2002 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-12003541

RESUMO

A stereoselective intramolecular 1,3-dipolar nitrone cycloaddition useful in the synthesis of chromanes is described. The reaction relies on the use of a chiral auxiliary on the nitrone partner. Key to the success of the reaction is the choice of auxiliary and the choice of Lewis acid catalyst. Utilizing an auxiliary with a pendant coordinating group, and Zn(OTf)(2) as the Lewis acid, diastereoselectivities up to 22:1 could be achieved.

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