RESUMEN
Several naturally occurring cyclopentenones, such as palmenones and nigrosporiones, exhibit antimicrobial activity. Herein we describe the antimicrobial activity of cyclopentenones and derivatives that can be easily accessed from biomass derivatives furfural and 5-hydroxymethylfurfural. Upon screening a range of functionalized trans-diamino-cyclopentenones (DCPs) and δ-lactone-fused cyclopentenones (LCPs), an oxime ether derivative of DCP was identified that exhibited remarkable antimicrobial activity against Gram-positive bacteria, including resistant strains such as methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE) strains.
Asunto(s)
Antibacterianos/farmacología , Ciclopentanos/farmacología , Enterococcus faecalis/efectos de los fármacos , Éter/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Oximas/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Ciclopentanos/síntesis química , Ciclopentanos/química , Relación Dosis-Respuesta a Droga , Éter/síntesis química , Éter/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Oximas/síntesis química , Oximas/química , Relación Estructura-Actividad , Resistencia a la Vancomicina/efectos de los fármacosRESUMEN
Previous investigation of the potent antileishmanial properties of antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines with biaryl side chains led to our development of a new clinical candidate for visceral leishmaniasis (DNDI-0690). Within a collaborative backup program, a racemic monoaryl lead (3) possessing comparable activity in mice but a greater hERG liability formed the starting point for our pursuit of efficacious second generation analogues having good solubility and safety. Asymmetric synthesis and appraisal of its enantiomers first established that chiral preferences for in vivo efficacy were species dependent and that neither form afforded a reduced hERG risk. However, in line with our findings in a structurally related series, less lipophilic heteroaryl ethers provided significant solubility enhancements (up to 16-fold) and concomitantly attenuated hERG inhibition. One promising pyridine derivative (49) displayed 100% oral bioavailability in mice and delivered a 96% parasite burden reduction when dosed at 50 mg/kg in a Leishmania donovani mouse model of visceral leishmaniasis.
Asunto(s)
Antiprotozoarios/síntesis química , Éter/síntesis química , Hidrocarburos Aromáticos/química , Leishmaniasis Visceral/tratamiento farmacológico , Oxazinas/química , Animales , Antiprotozoarios/administración & dosificación , Antiprotozoarios/farmacocinética , Cricetinae , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Éter/administración & dosificación , Éter/farmacocinética , Femenino , Humanos , Leishmania donovani/efectos de los fármacos , Masculino , Ratones , Pruebas de Sensibilidad Parasitaria , Piridinas/química , Solubilidad , Relación Estructura-ActividadRESUMEN
Construction of a focused library of polycyclic ether-benzopyrans was undertaken in order to discover new therapeutic compounds that affect Leishmania growth and infectivity. This is especially of interest since there are few drug therapies for leishmaniasis that do not have serious drawbacks such high cost, side effects, and emerging drug resistance. The construction of these polycyclic ether-benzopyrans utilized an acetoxypyranone-alkene [5+2] cycloaddition and the Suzuki-Miyaura cross-coupling. The multi-gram quantity of the requisite aryl bromide was obtained followed by effective Pd-catalyzed coupling with boronic acid derivatives. Compounds were tested in vitro using the parasitic protozoan, Leishmania tarentolae. Effects of concentration, time, and exposure to light were evaluated. In addition, the effects on secreted acid phosphatase activity and nitric oxide production were investigated, since both have been implicated in parasite infectivity. The data presented herein are indicative of disruption of the Leishmania tarentolae and thus provide impetus for the development and testing of a more extensive library.
Asunto(s)
Benzopiranos/síntesis química , Benzopiranos/farmacología , Éter/síntesis química , Éter/farmacología , Leishmania/efectos de los fármacos , Compuestos Policíclicos/síntesis química , Compuestos Policíclicos/farmacología , Fosfatasa Ácida/metabolismo , Benzopiranos/química , Bromuros/química , Catálisis , Recuento de Células , Reacción de Cicloadición , Pruebas de Enzimas , Leishmania/enzimología , Leishmania/crecimiento & desarrollo , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Paladio/química , Compuestos Policíclicos/químicaRESUMEN
Parthenolide (PTL) strongly inhibits the detyrosination of microtubules and accelerates neuronal growth. In order to access cyclic ether derivatives of PTL, ring-closing metathesis (RCM) was investigated in comparison to intramolecular sulfone alkylation. Incompatibility of RCM with epoxides was found in this setting. Biological evaluation for tubulin carboxypeptidase inhibition indicated that the epoxide is crucial for parthenolide's activity.
Asunto(s)
Carboxipeptidasas/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Éter/farmacología , Microtúbulos/efectos de los fármacos , Neuronas/efectos de los fármacos , Sesquiterpenos/farmacología , Adulto , Carboxipeptidasas/metabolismo , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Éter/síntesis química , Éter/química , Humanos , Estructura Molecular , Sesquiterpenos/síntesis química , Sesquiterpenos/química , Relación Estructura-Actividad , Tanacetum parthenium/químicaRESUMEN
This study aims to investigate the production of ethylene and diethyl ether from ethanol via catalytic dehydration using Si- and Al-based catalysts with Pd modification. First, six catalysts including H-beta zeolite (HBZ), mixed phases of γ-χ-Al2O3 (M-Al) and γ-Al2O3 (G-Al) with and without Pd modification (0.5 wt%) were prepared. The catalytic dehydration of vaporized ethanol at temperature ranging from 200 to 400°C was performed over the catalysts. For ethylene production, the most promising catalyst is HBZ (giving ethylene yield of ca. 99% at 400°C), whereas Pd modification has no significant effect on ethylene production. Considering the production of diethyl ether, it is produced at lower temperature (ca. 250°C) than that of ethylene. The most active catalyst to produce diethyl ether is HBZ with Pd modification (giving diethyl ether yield of ca. 48% at 250°C). Thus, increased diethyl ether yield can be achieved with Pd modification at low temperature for the HBZ catalyst. Other catalysts such as M-Al and G-Al can also produce significant amounts of ethylene. To elucidate the effect of Pd modification on these catalysts, different characterization techniques such as nitrogen physisorption (BET and BJH methods), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS) and ammonia temperature-programmed desorption were performed and further discussed in more detail.
Asunto(s)
Compuestos de Aluminio/química , Etanol/química , Éter/síntesis química , Etilenos/síntesis química , Paladio/química , Compuestos de Silicona/química , Catálisis , Química Orgánica/métodos , Desecación , Temperatura , VolatilizaciónRESUMEN
AIM: The aim of the study was to explore the growth inhibitory effect of myricanol 5-fluorobenzyloxy ether (5FEM) and the underlying mechanism in human leukemic cells HL-60. MATERIALS & METHODS: 5FEM was obtained by chemical modification of myricanol with fluorobenzyloxy ether at the OH(5) position. The cytotoxicity, cell apoptosis, cell cycle and the expression of key apoptosis-related genes in HL-60 were evaluated. RESULTS & CONCLUSION: 5FEM can significantly inhibited growth of HL-60 cells, increased the G2/M population and upregulated the expression of Bax, Fas, FasL, caspase-9 and p21 and downregulated that of Bcl-2 and survivin. The results enhance our understanding of 5FEM and aid the discovery of novel myricanol derivatives as potential antitumor agents.
Asunto(s)
Antineoplásicos/química , Diarilheptanoides/química , Éter/química , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 9/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Diarilheptanoides/síntesis química , Diarilheptanoides/toxicidad , Regulación hacia Abajo/efectos de los fármacos , Éter/síntesis química , Éter/farmacología , Proteína Ligando Fas/genética , Proteína Ligando Fas/metabolismo , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Células HL-60 , Humanos , Leucemia , Puntos de Control de la Fase M del Ciclo Celular/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo , Receptor fas/genética , Receptor fas/metabolismoRESUMEN
A new library of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl ether derivatives (1-23) were synthesized and characterized by EI-MS and 1H NMR, and screened for their α-amylase inhibitory activity. Out of twenty-three derivatives, two molecules 19 (IC50=0.38±0.82µM) and 23 (IC50=1.66±0.14µM), showed excellent activity whereas the remaining compounds, except 10 and 17, showed good to moderate inhibition in the range of IC50=1.77-2.98µM when compared with the standard acarbose (IC50=1.66±0.1µM). A plausible structure-activity relationship has also been presented. In addition, in silico studies was carried out in order to rationalize the binding interaction of compounds with the active site of enzyme.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Éter/farmacología , Imidazoles/farmacología , Simulación del Acoplamiento Molecular , alfa-Amilasas/antagonistas & inhibidores , Animales , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Éter/síntesis química , Éter/química , Imidazoles/síntesis química , Imidazoles/química , Estructura Molecular , Relación Estructura-Actividad , Porcinos , alfa-Amilasas/metabolismoRESUMEN
Growing concern with the effects of CO2 emissions due to the combustion of petroleum-based transportation fuels has motivated the search for means to increase engine efficiency. The discovery of ethers with low viscosity presents an important opportunity to improve engine efficiency and fuel economy. We show here a strategy for the catalytic synthesis of such ethers by reductive etherification/O-alkylation of alcohols using building blocks that can be sourced from biomass. We find that long-chain branched ethers have several properties that make them superior lubricants to the mineral oil and synthetic base oils used today. These ethers provide a class of potentially renewable alternatives to conventional lubricants produced from petroleum and may contribute to the reduction of greenhouse gases associated with vehicle emissions.
Asunto(s)
Biomasa , Éter/síntesis química , Lubricantes/síntesis química , Emisiones de Vehículos , Alcoholes , Automóviles , Estructura MolecularRESUMEN
In the present study, the catalytic dehydration of ethanol over H-beta zeolite (HBZ) catalyst with ruthenium (Ru-HBZ) and platinum (Pt-HBZ) modification was investigated. Upon the reaction temperature between 200 and 400°C, it revealed that ethanol conversion and ethylene selectivity increased with increasing temperature for both Ru and Pt modification. At lower temperature (200 to 250°C), diethyl ether (DEE) was the major product. It was found that Ru and Pt modification on HBZ catalyst can result in increased DEE yield at low reaction temperature due to increased ethanol conversion without a significant change in DEE selectivity. By comparing the DEE yield of all catalysts in this study, the Ru-HBZ catalyst apparently exhibited the highest DEE yield (ca. 47%) at 250°C. However, at temperature from 350 to 400°C, the effect of Ru and Pt was less pronounced on ethylene yield. With various characterization techniques, the effects of Ru and Pt modification on HBZ catalyst were elucidated. It revealed that Ru and Pt were present in the highly dispersed forms and well distributed in the catalyst granules. It appeared that the weak acid sites measured by NH3 temperature-programmed desorption technique also decreased with Ru and Pt promotion. Thus, the increased DEE yields with the Ru and Pt modification can be attributed to the presence of optimal weak acid sites leading to increased intrinsic activity of the catalysts. It can be concluded that the modification of Ru and Pt on HBZ catalyst can improve the DEE yields by ca. 10%.
Asunto(s)
Etanol/química , Éter/síntesis química , Platino (Metal)/química , Rutenio/química , Zeolitas/química , Catálisis , Deshidratación , Éter/química , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
A set of diphenyl ether derivatives bearing different heterocycles were synthesized from 4-phenoxybenzohydrazide 1 in good yield. Synthesized compounds were screened against a broad panel of viruses in different cell cultures and some of the synthesized compounds showed promising antiviral properties.
Asunto(s)
Compuestos de Bifenilo/síntesis química , Compuestos de Bifenilo/farmacología , Éter/síntesis química , Éter/farmacología , Virus/efectos de los fármacos , Antivirales/síntesis química , Antivirales/química , Antivirales/farmacología , Bioensayo , Compuestos de Bifenilo/química , Células Cultivadas , Evaluación Preclínica de Medicamentos , Éter/química , Humanos , Modelos Moleculares , Estructura Molecular , Pirazoles/química , Pirazoles/farmacología , Piridinas/química , Piridinas/farmacologíaRESUMEN
A series of benzoyl diarylamine/ether derivatives were designed, synthesized, and evaluated for their activity against human immunodeficiency virus (HIV) in MT-4 cells. Three compounds (3b, 5a, and 6a1) exhibited moderate activities against wild-type (wt) HIV-1 with EC50 values ranging from 11 to 56 µm. Among them, compound 5a was the most potent inhibitor with a novel chemical skeleton, affording a new lead compound for further molecular optimization. An enzyme assay was also implemented to confirm the binding target of the active compounds represented by 6a1. Molecular simulation studies on compound 5a, 6a1, and 7a4 were carried out to understand their binding mode with wt HIV-1 reverse transcriptase (RT) and provided useful information for further rational design of NNRTIs.
Asunto(s)
Compuestos de Anilina/química , Compuestos de Anilina/farmacología , Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacología , Éter/análogos & derivados , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa/química , Inhibidores de la Transcriptasa Inversa/farmacología , Compuestos de Anilina/síntesis química , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/farmacocinética , Línea Celular , Diseño de Fármacos , Éter/síntesis química , Éter/química , Éter/farmacología , VIH-1/enzimología , Humanos , Modelos Moleculares , Inhibidores de la Transcriptasa Inversa/síntesis químicaRESUMEN
Azole-containing selenoethers, 1,5-bis(3,5-dimethylpyrazol-1-yl)-3-selena pentane and 1,3-bis(1,2,3-benzotriazol-1-yl)-2-selena propane were prepared by the reaction of corresponding tosylate or chloride with sodium selenide generated in situ from elemental selenium and sodium formaldehydesulfoxylate (rongalite).
Asunto(s)
Química Orgánica/métodos , Éter/síntesis química , Pirazoles/química , Triazoles/química , Cristalografía por Rayos X , Éter/química , Conformación Molecular , Selenio/químicaRESUMEN
We describe the syntheses of the proposed structure of diphenyl ether oxyneolignan, apteniol A and its derivatives. The diphenyl ether moiety of proposed apteniol A was formed via Ullmann ether synthesis, but the spectral data of the synthesized apteniol A did not agree with that in previous studies. The dimethyl ester derivative of the proposed apteniol A was found to enhance neurite outgrowth in PC12 cells and inhibit antigen-induced degranulation in RBL-2H3 cells.
Asunto(s)
Éter/química , Lignanos/química , Neuritas/efectos de los fármacos , Animales , Degranulación de la Célula/efectos de los fármacos , Degranulación de la Célula/inmunología , Éter/síntesis química , Éter/farmacología , Lignanos/síntesis química , Lignanos/farmacología , Mastocitos/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Células PC12 , RatasRESUMEN
A one-step Bronsted acid-catalyzed synthetic methodology leading to 3-(alkoxymethylene)indolin-2-ones was developed starting from easily accessible 2-hydroxyindole-3-carboxaldehydes. The procedure simply involves a treatment of differently substituted 2-hydroxyindole-3-carboxaldehydes with various alcohols (primary/secondary/tertiary/allyl/propargyl/benzyl) in the presence of a catalytic amount of Bronsted acids such as [Formula: see text]-toluenesulfonic acid and trifluroacetic acid. A series of 19 indolin-2-one-based enol-ethers were synthesized in excellent yields, which implies the general character of our methodology. The enol-ethers produced could be used as a useful building block for the synthesis of indole-based heterocycles.
Asunto(s)
Ácidos/química , Aldehídos/química , Éter/síntesis química , Indoles/química , Catálisis , Estructura MolecularRESUMEN
Amphiphilic linear and dumbbell-shaped poly(ethylene glycol)-poly(lactide-co-glycolide) (PEG-PLGA) copolymers were simply synthesized by the ring-opening polymerization of lactide and glycolide using PEG or tetrahydroxyl-functionalized PEG as the macroinitiator and stannous octoate as the catalyst. The copolymers spontaneously self-assembled into spherical micelles in phosphate-buffered saline at pH 7.4. The self-assembly behavior was dependent on both the polymeric topology and composition. Doxorubicin (DOX), an anthracycline antitumor drug, was loaded into micelles through nanoprecipitation. The in vitro release behavior could be adjusted by regulating the topology or composition of the copolymer, or the pH of the release medium. The effective intracellular DOX release from DOX-loaded micelles was confirmed by confocal laser scanning microscopy and flow cytometry in vitro. DOX-loaded micelles displayed great cellular proliferation inhibition efficacies after incubation for 24, 48 or 72 h. The hemolysis ratio of DOX was significantly reduced by the presence of copolymer. These properties indicated that the micelles derived from linear or dumbbell-shaped copolymers were promising candidates as smart antitumor drug carriers for malignancy therapy.
Asunto(s)
Antineoplásicos/farmacología , Sistemas de Liberación de Medicamentos , Éter/química , Micelas , Poliésteres/química , Polietilenglicoles/química , Poliglactina 910/química , Animales , Muerte Celular/efectos de los fármacos , Línea Celular , Cromatografía en Gel , Doxorrubicina/farmacología , Eritrocitos/efectos de los fármacos , Éter/síntesis química , Citometría de Flujo , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Ratones , Microscopía Electrónica de Transmisión , Poliésteres/síntesis química , Polietilenglicoles/síntesis química , Poliglactina 910/síntesis química , Conejos , Soluciones , Espectrometría de Fluorescencia , Espectroscopía Infrarroja por Transformada de Fourier , Tensoactivos/síntesis química , Tensoactivos/químicaRESUMEN
BACKGROUND: The heterogeneity of liver cancer, in particular hepatocellular carcinoma (HCC), portrays the requirement of multiple targets for both its treatment and prevention. Multifaceted agents, minimally or non-toxic for normal hepatocytes, are required to address the molecular diversity of HCC, including the resistance of putative liver cancer stem cells to chemotherapy. METHODS: We designed and synthesized two fatty acid ethers of isopropylamino propanol, C16:0-AIP-1 and C18:1-AIP-2 (jointly named AIPs), and evaluated their anti-proliferative effects on the human HCC cell line Huh7 and the murine hepatoma cell line BNL 1MEA.7R.1, both in vitro and in an in vivo allograft mouse model. RESULTS: We found that AIP-1 and AIP-2 inhibited proliferation and caused cell death in both Huh7 and BNL 1MEA.7R.1 cells. Importantly, AIP-1 and AIP-2 were found to block the activation of putative liver cancer stem cells as manifested by suppression of clonal 'carcinosphere' development in growth factor-free and anchorage-free medium. The AIPs exhibited a relatively low toxicity against normal human or rat hepatocytes in primary cultures. In addition, we found that the AIPs utilized multifaceted pathways that mediate both autophagy and apoptosis in HCC, including the inhibition of AKTs and CAMK-1. In immune-competent mice, the AIPs significantly reduced BNL 1MEA.7R.1 cell-driven tumor allograft development, with a higher efficiency than sorafenib. A combination of AIP-1 + AIP-2 was most effective in reducing the tumor allograft incidence. CONCLUSIONS: AIPs represent a novel class of simple fatty acid derivatives that are effective against liver tumors via diverse pathways. They show a low toxicity towards normal hepatocytes. The addition of AIPs may represent a new avenue towards the management of chronic liver injury and, ultimately, the prevention and treatment of HCC.
Asunto(s)
Amidas/farmacología , Éter/farmacología , Ácidos Grasos/farmacología , Neoplasias Hepáticas/patología , Trasplante de Neoplasias , Amidas/síntesis química , Amidas/química , Amidas/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Sistema Libre de Células , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Éter/síntesis química , Éter/química , Éter/uso terapéutico , Ácidos Grasos/uso terapéutico , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Ratones , Inhibidores de Proteínas Quinasas/farmacología , Proteolisis/efectos de los fármacos , Espectrina/metabolismo , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismo , Esferoides Celulares/patologíaRESUMEN
We report a series of new 9-oxime ether non-ketolides, including 3-hydroxyl, 3-O-acyl and 3-O-alkyl clarithromycin derivatives, and thiophene-containing ketolides 1b-1d. Unlike previously reported ketolide 1a, none of them is comparable to telithromycin. A molecular modeling study was performed to gain insight into the binding mode of alkylides 17-20 with bacterial rRNA and to rationalize the great disparity of their SAR. The 3-O-sidechains of 19 and 20 point to the so-called hydrophilic side of the macrolide ring, as seen in clarithromycin. In contrast, the 3-O-sidechains of 17 and 18 bend to the backside, the so-called hydrophobic side of the macrolide ring. The results clearly indicated the alkylides with improved antibacterial activity might possess a novel binding mode, which is different from clarithromycin and the alkylides with poor activity.
Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Eritromicina/análogos & derivados , Oximas/síntesis química , Oximas/farmacología , ARN Ribosómico/metabolismo , Antibacterianos/química , Claritromicina/química , Claritromicina/farmacología , Eritromicina/síntesis química , Éter/síntesis química , Éter/química , Éter/farmacología , Cetólidos/síntesis química , Cetólidos/química , Cetólidos/farmacología , Modelos Moleculares , Oximas/química , ARN Bacteriano/metabolismoRESUMEN
A highly efficient total synthesis of the 11-membered cyclic aspercyclides A (1) and B (2) has been achieved by chemo- and regioselective intramolecular oxidative C-O bond formation from differently substituted diphenols.
Asunto(s)
Éter/síntesis química , Lactonas/síntesis química , Compuestos Macrocíclicos/síntesis química , Aspergillus/química , Éter/química , Lactonas/química , Compuestos Macrocíclicos/química , Estructura Molecular , Oxidación-Reducción , Fenoles/química , EstereoisomerismoRESUMEN
A focused library of twenty-one cationic poly(amino ethers) was synthesized following ring-opening polymerization of two diglycidyl ethers by different oligoamines. The polymers were screened in parallel for plasmid DNA (pDNA) delivery, and transgene expression efficacies of individual polymers were compared to those of 25 kDa polyethylenimine (PEI), a current standard for polymer-mediated transgene delivery. Seven lead polymers that demonstrated higher transgene expression than PEI in pancreatic and prostate cancer cells lines were identified from the screen. All seven lead polymers showed highest transgene expression at a polymer:pDNA weight ratio of 5:1 in the MIA PaCa-2 pancreatic cancer cell line. Among the conditions studied, transgene expression efficacy correlated with minimal polymer cytotoxicity but not polyplex sizes. In addition, this study indicated that methylene spacing between amine centers in the monomers, amine content, and molecular weight of the polymers are all significant factors and should be considered when designing polymers for transgene delivery. A lead effective polymer was employed for coating gold nanorods, leading to theranostic nanoassemblies that possess combined transgene delivery and optical imaging capabilities, leading to potential theranostic systems.
Asunto(s)
Éter/uso terapéutico , Técnicas de Transferencia de Gen , Oro/química , Nanotubos/química , Poliaminas/uso terapéutico , Transgenes/genética , Aminas/química , Muerte Celular , Línea Celular Tumoral , Diagnóstico por Imagen , Éter/síntesis química , Éter/química , Expresión Génica , Humanos , Hidrodinámica , Luciferasas/metabolismo , Peso Molecular , Tamaño de la Partícula , Poliaminas/síntesis química , Poliaminas/química , Espectrofotometría Ultravioleta , Electricidad EstáticaRESUMEN
Synthesis of new antitumor ether glycerolipids with various heterocyclic nitrogen-containing bases as polar domains is described. We propose synthetic scheme for cationic lipids containing aliphatic short-chain substituents in the heterocyclic polar head.