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1.
Nano Lett ; 23(8): 3144-3151, 2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-37026614

RESUMEN

Group IV monochalcogenides have recently shown great potential for their thermoelectric, ferroelectric, and other intriguing properties. The electrical properties of group IV monochalcogenides exhibit a strong dependence on the chalcogen type. For example, GeTe exhibits high doping concentration, whereas S/Se-based chalcogenides are semiconductors with sizable bandgaps. Here, we investigate the electrical and thermoelectric properties of γ-GeSe, a recently identified polymorph of GeSe. γ-GeSe exhibits high electrical conductivity (∼106 S/m) and a relatively low Seebeck coefficient (9.4 µV/K at room temperature) owing to its high p-doping level (5 × 1021 cm-3), which is in stark contrast to other known GeSe polymorphs. Elemental analysis and first-principles calculations confirm that the abundant formation of Ge vacancies leads to the high p-doping concentration. The magnetoresistance measurements also reveal weak antilocalization because of spin-orbit coupling in the crystal. Our results demonstrate that γ-GeSe is a unique polymorph in which the modified local bonding configuration leads to substantially different physical properties.

2.
Bioorg Med Chem Lett ; 20(19): 5709-12, 2010 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-20797857

RESUMEN

In spite of potent antiviral activity, suboptimal physicochemical properties of aryl diketo acids (ADKs) necessitates modification of the core 1,3-diketo acid functionality into a novel scaffold. As the metal-binding affinity of the diketo acid is the key to the antiviral activity of ADKs, we anticipated 3,5-dihydroxy-4-oxo arrangement of galangin scaffold would serve as an excellent mimic for the diketo acid functionality. In this study, through synthesis and biological evaluation of various galangin derivatives, we have shown that the diketo acid functionality can be successfully replaced with the galangin scaffold by specific combination of the substituents to result in identification of a novel galangin derivative (3s) with anti-HCV activity (EC(50)=0.9 µM) comparable to the ADK counterpart.


Asunto(s)
Antivirales/química , Flavonoides/química , Cetoácidos/química , Antivirales/síntesis química , Antivirales/farmacología , Flavonoides/síntesis química , Flavonoides/farmacología , Hepacivirus/efectos de los fármacos , Inhibidores de Proteasas/síntesis química , Inhibidores de Proteasas/química , Inhibidores de Proteasas/farmacología , Relación Estructura-Actividad , Proteínas no Estructurales Virales/antagonistas & inhibidores , Proteínas no Estructurales Virales/metabolismo
3.
Bioorg Med Chem Lett ; 19(16): 4538-41, 2009 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-19625187

RESUMEN

Aryl diketoacids have been identified as the first SARS-CoV NTPase/helicase inhibitors with a distinct pharmacophore featuring an arylmethyl group attached to a diketoacid. In order to search for the pharmacophore space around the diketoacid core, three classes of dihydroxychromone derivatives were prepared. Based on SAR study, an extended feature of the pharmacophore model of SARS-CoV NTPase/helicase was proposed which is constituted of a diketoacid core, a hydrophobic arylmethyl substituent, and a free catechol unit.


Asunto(s)
Antivirales/química , Cromonas/química , ADN Helicasas/antagonistas & inhibidores , Inhibidores Enzimáticos/química , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/enzimología , Antivirales/síntesis química , Antivirales/farmacología , Catecoles/química , Cromonas/síntesis química , Cromonas/farmacología , ADN Helicasas/metabolismo , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Relación Estructura-Actividad
4.
Bioorg Med Chem Lett ; 19(6): 1636-8, 2009 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-19233643

RESUMEN

As anti-HCV aryl diketoacids (ADK) are good metal chelators, we anticipated that ADKs might serve as potential inhibitors of SARS CoV (SCV) NTPase/helicase (Hel) by mimicking the binding modes of the bismuth complexes which effectively competes for the Zn(2+) ion binding sites in SCV Hel thereby disrupting and inhibiting both the NTPase and helicase activities. Phosphate release assay and FRET-based assay of the ADK analogues showed that the ADKs selectively inhibit the duplex DNA-unwinding activity without significant impact on the helicase ATPase activity. Also, antiviral activities of the ADKs were shown dependent upon the substituent. Taken together, these results suggest that there might be ADK-specific binding site in the SCV Hel, which warrants further investigations with diverse ADKs to provide valuable insights into rational design of specific SCV Hel inhibitors.


Asunto(s)
Química Farmacéutica/métodos , ADN Helicasas/química , ADN/química , Cetoácidos/química , Nucleósido-Trifosfatasa/química , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/enzimología , Sitios de Unión , Diseño de Fármacos , Transferencia Resonante de Energía de Fluorescencia , Concentración 50 Inhibidora , Iones , Modelos Químicos , Fosfatos/química , Relación Estructura-Actividad , Zinc/química
6.
J Control Release ; 226: 258-67, 2016 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-26812006

RESUMEN

The use of computed tomography (CT) for vascular imaging is critical in medical emergencies requiring urgent diagnostic decisions, such as cerebral ischemia and many cardiovascular diseases. Small-molecule iodinated contrast media are often injected intravenously as radiopaque agents during CT imaging to achieve high contrast enhancement of vascular systems. The rapid excretion rate of these agents is overcome by injecting a significantly high dose of iodine, which can have serious side effects. Here we report a simple method to prepare blood-pool contrast agents for CT based on dendrimers for the first time using tetraiodobenzene derivatives as potent radiopaque moieties. Excellent in vivo safety has been demonstrated for these small (13-22nm) unimolecular water-soluble dendritic contrast agents, which exhibit high contrast enhancement in the blood-pool and effectively extend their blood half-lives. Our method is applicable to virtually any scaffold with suitable surface groups and may fulfill the current need for safer, next-generation iodinated CT contrast agents.


Asunto(s)
Medios de Contraste/química , Dendrímeros/química , Yodobencenos/química , Nylons/química , Tomografía Computarizada por Rayos X , Animales , Medios de Contraste/efectos adversos , Medios de Contraste/farmacocinética , Dendrímeros/efectos adversos , Dendrímeros/farmacocinética , Células HeLa , Humanos , Yodobencenos/efectos adversos , Yodobencenos/farmacocinética , Masculino , Ratones Endogámicos C57BL , Nylons/efectos adversos , Nylons/farmacocinética
7.
Chem Commun (Camb) ; 49(68): 7528-30, 2013 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-23863959

RESUMEN

A small 29 nm monodispersed silica nanoparticle 1a was synthesized as a diarylethene-based reversible fluorescence photoswitch by copolymerizing silane precursors in one-pot including 3a and 4. Reversible photoswitching of nanoparticle 1a was successfully achieved in living cells to show its potential as a highly distinguishable and safe fluorescence probe for cell tracking.


Asunto(s)
Etilenos/química , Fluorescencia , Nanopartículas/química , Dióxido de Silicio/síntesis química , Células Madre/química , Células HeLa , Humanos , Tamaño de la Partícula , Procesos Fotoquímicos , Dióxido de Silicio/química , Propiedades de Superficie
8.
Eur J Med Chem ; 46(11): 5698-704, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21925774

RESUMEN

In this study, as a bioisosteric alternative scaffold of the antiviral aryl diketoacids (ADKs), we used 5-hydroxychromone on which two arylmethyloxy substituents were installed. The 5-hydroxychromones (5b-5g) thus prepared showed anti-HCV activity and, depending on the aromatic substituents on the 2-arylmethyloxy moiety, some of the derivatives (5b-5f) were also active against SCV. In addition, unlike the ADKs which showed selective inhibition against the helicase activity of the SCV NTPase/helicase, the 5-hydroxychromones (5b-5f) were active against both NTPase and helicase activities of the target enzyme. Among those, 3-iodobenzyloxy-substituted derivative 5e showed the most potent activity against HCV (EC(50) = 4 µM) as well as SCV (IC(50) = 4 µM for ATPase activity, 11 µM for helicase activity) and this might be used as a platform structure for future development of the multi-target or broad-spectrum antivirals.


Asunto(s)
Antivirales/síntesis química , Antivirales/farmacología , Cromonas/síntesis química , Cromonas/farmacología , Hepacivirus/efectos de los fármacos , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/efectos de los fármacos , Antivirales/química , Antivirales/toxicidad , Línea Celular Tumoral , Cromonas/química , Cromonas/toxicidad , Humanos , Concentración 50 Inhibidora
9.
J Med Chem ; 53(24): 8597-607, 2010 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-21090565

RESUMEN

In order to increase stability of quercetin, its metabolically and chemically susceptible hydroxyl groups 7-OH and 3-OH respectively were transiently blocked with a pivaloxymethyl (POM) promoiety to provide two novel quercetin conjugates [7-O-POM-Q, 3-O-POM-Q]. In the absence of stabilizer (ascorbic acid), the synthesized conjugates showed significantly increased stability in cell culture media [t(½) = 4 h, 52 h] compared with quercetin (t(½) < 30 min) and quercetin prodrug 1 (t(½) = 0.8 h). In addition, the quercetin conjugate 2 underwent efficient cellular uptake and intracellular levels of its hydrolysis product, quercetin, were maintained up to 12 h. Stability and intracellular accumulation of were demonstrated by its stabilizer-independent cytostatic effect and induction of apoptotic cell death. Even though was more stable than, it failed to penetrate cell membranes. However, the remarkable stability of warrants further investigation of quercetin conjugates with various promoieties at the 3-OH position.


Asunto(s)
Antineoplásicos/síntesis química , Profármacos/síntesis química , Quercetina/análogos & derivados , Quercetina/síntesis química , Antineoplásicos/farmacología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Permeabilidad de la Membrana Celular , Supervivencia Celular/efectos de los fármacos , Medios de Cultivo , Ensayos de Selección de Medicamentos Antitumorales , Estabilidad de Medicamentos , Humanos , Hidrólisis , Profármacos/farmacología , Quercetina/farmacología , Solubilidad , Estereoisomerismo , Relación Estructura-Actividad
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