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1.
Carbohydr Res ; 498: 108178, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33045644

RESUMO

An efficient route for the synthesis of benzimidazole nucleosides 1-8 from readily available d-glucose via 3,5-dihydroxy-1,2-O-isopropylidene-α-d-ribofuranose and 3-azido-3-deoxy-1,2-O-isopropylidene-α-d-xylofuranose intermediates has been adopted. Ribofuranosyl nucleosides 1-4 with different benzimidazole bases, and 3'-deoxy-3'-azido-ribofuranosyl nucleosides 5-8, as another series, were obtained. All these newly synthesized analogs were evaluated for anticancer activity using MDA-MB-231 cell line. Among the differently substituted derivatives, 3'-azide substituted nucleosides (5-8) are more potent compared to ribofuranosyl analogs 1-4. The C-3'-azido analog 8 having anthryl group at 2-position of nucleobase show almost similar potency as that of standard etoposide.

3.
Adv Pharmacol Sci ; 2019: 9080279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30886631

RESUMO

Rapid, eco-friendly, and cost-effective one-pot synthesis of copper nanoparticles is reported here using medicinal plants like Gnidia glauca and Plumbago zeylanica. Aqueous extracts of flower, leaf, and stem of G. glauca and leaves of P. zeylanica were prepared which could effectively reduce Cu2+ ions to CuNPs within 5 h at 100°C which were further characterized using UV-visible spectroscopy, field emission scanning electron microscopy, high-resolution transmission electron microscopy, energy dispersive spectroscopy, dynamic light scattering, X-ray diffraction, and Fourier-transform infrared spectroscopy. Further, the CuNPs were checked for antidiabetic activity using porcine pancreatic α-amylase and α-glucosidase inhibition followed by evaluation of mechanism using circular dichroism spectroscopy. CuNPs were found to be predominantly spherical in nature with a diameter ranging from 1 to 5 nm. The phenolics and flavonoids in the extracts might play a critical role in the synthesis and stabilization process. Significant change in the peak at ∼1095 cm-1 corresponding to C-O-C bond in ether was observed. CuNPs could inhibit porcine pancreatic α-amylase up to 30% to 50%, while they exhibited a more significant inhibition of α-glucosidase from 70% to 88%. The mechanism of enzyme inhibition was attributed due to the conformational change owing to drastic alteration of secondary structure by CuNPs. This is the first study of its kind that provides a strong scientific rationale that phytogenic CuNPs synthesized using G. glauca and P. zeylanica can be considered to develop candidate antidiabetic nanomedicine.

4.
ACS Comb Sci ; 21(3): 105-148, 2019 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-30645098

RESUMO

The Biginelli product, dihydropyrimidinone (DHPM) core, and its derivatives are of immense biological importance. There are several methods reported as modifications to the original Biginelli reaction. Among them, many involve the use of different catalysts. Also, among the advancements that have been made to the Biginelli reaction, improvements in product yields, less hazardous reaction conditions, and simplified isolation of products from the reaction predominate. Recently, solid-phase synthetic protocols have attracted the research community for improved yields, simplified product purification, recyclability of the solid support, which forms a special economic approach for Biginelli reaction. The present Review highlights the role of polymer-supported catalysts in Biginelli reaction, which may involve organic, inorganic, or hybrid polymers as support for catalysts. A few of the schemes involve magnetically recoverable catalysts where work up provides green approach relative to traditional methods. Some research groups used polymer-catalyst nanocomposites and polymer-supported ionic liquids as catalyst. Solvent-free, an ultrasound or microwave-assisted Biginelli reactions with polymer-supported catalysts are also reported.


Assuntos
Nanocompostos/química , Polímeros/química , Pirimidinonas/síntese química , Técnicas de Síntese em Fase Sólida/métodos , Catálise , Líquidos Iônicos/química , Micro-Ondas , Estrutura Molecular , Solventes/química , Propriedades de Superfície
5.
Bioorg Med Chem Lett ; 27(23): 5291-5295, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29074258

RESUMO

An efficient and practical strategy for the synthesis of unknown azetidine iminosugars (2S,3R,4S)-2-((R)-1,2-dihydroxyethyl)-3-hydroxy-4-(hydroxymethyl)azetidine 2, (2S,3r,4R)-3-hydroxy-2,4-bis(hydroxymethyl)azetidine 3 and (2S,3R,4S)-3-hydroxy-4-(hydroxymethyl)-N-methylazetidine-2-carboxylic acid 4, starting from the d-glucose has been reported. The methodology involves preparation of the 3-amino-N-benzyloxycarbonyl-3-deoxy-6-O-tert-butyldimethylsillyl-1,2-O-isopropylidene-α-d-glucofuranose 9, which was converted to the C-5-OMs derivative 11. Intramolecular nucleophilic displacement of the C-5-OMs group with in situ generated 3-amino functionality provided the required key azetidine ring skeletons 10 with additional hydroxymethyl group. Removal of 1,2-acetonide protection, followed by reduction and hydrogenolysis afforded azetidine iminosugar 2. Alternatively, removal of 1,2-acetonide group and chopping of C1-anomeric carbon gave C2-aldehyde that on reduction or oxidation followed by hydrogenolysis gave 2,4-bis(hydroxymethyl) azetidine iminosugars 3 and N-methylazetidine-2-carboxylic acid 4 respectively. The glycosidase inhibitory activity of 2-4 iminosugars was screened against various glycosidase enzymes and compared with a standard miglitol. Amongst synthesized targets, the compound 2 was found to be more potent amyloglucosidase inhibitor than miglitol. These results were supported by molecular docking studies.


Assuntos
Inibidores Enzimáticos/farmacologia , Glicosídeo Hidrolases/antagonistas & inibidores , Imino Açúcares/farmacologia , Simulação de Acoplamento Molecular , Aspergillus niger/enzimologia , Canavalia/enzimologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Escherichia coli/enzimologia , Glicosídeo Hidrolases/metabolismo , Hidroxilação , Imino Açúcares/síntese química , Imino Açúcares/química , Estrutura Molecular , Relação Estrutura-Atividade , alfa-Galactosidase/antagonistas & inibidores , alfa-Galactosidase/metabolismo , alfa-Manosidase/antagonistas & inibidores , alfa-Manosidase/metabolismo
6.
Org Biomol Chem ; 14(17): 4136-45, 2016 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-27074628

RESUMO

An efficient route was developed for synthesis of bicyclic benzimidazole nucleosides from readily available d-glucose. The key reactions were Vörbruggen glycosylation and ring closing metathesis (RCM). Primarily, to understand the mode of DNA binding, we performed a molecular docking study and the binding was found to be in the minor groove region. Based on the proposed binding model, UV-visible and fluorescence spectroscopic techniques using calf thymus DNA (CT-DNA) demonstrated a non-intercalative mode of binding. Antiproliferative activity of nucleosides was tested against MCF-7 and MDA-MB-231 breast cancer cell lines and found to be active at low micromolar concentrations. Compounds and displayed significant antiproliferative activity as compared to and with the reference anticancer drug, doxorubicin. Cell cycle analysis showed that nucleoside induced cell cycle arrest at the S-phase. Confocal microscopy has been performed to validate the induction of cellular apoptosis. Based on these findings, such modified bicyclic benzimidazole nucleosides will make a significant contribution to the development of anticancer drugs.


Assuntos
Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , DNA de Neoplasias/efeitos dos fármacos , Nucleosídeos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Benzimidazóis/síntese química , Benzimidazóis/química , Sítios de Ligação/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Conformação Molecular , Simulação de Acoplamento Molecular , Nucleosídeos/síntese química , Nucleosídeos/química , Relação Estrutura-Atividade
7.
Chemistry ; 22(23): 7917-23, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27113075

RESUMO

The base-pairing properties of 5-mercuricytosine have been explored at the monomer level by NMR titrations and at the oligonucleotide level by melting temperature measurements. The NMR studies revealed a relatively high affinity for guanine, hypoxanthine, and uridine, that is, bases that are deprotonated upon coordination of Hg(II) . Within an oligonucleotide duplex, 5-mercuricytosine formed Hg(II) -mediated base pairs with thymine and guanine. In the former case, the duplex formed was as stable as the respective duplex comprising solely Watson-Crick base pairs. Based on detailed thermodynamic analysis of the melting curves, the stabilization by the Hg(II) -mediated base pairs may be attributed to a comparatively low entropic penalty of hybridization.


Assuntos
Pareamento de Bases , Citosina/análogos & derivados , Mercúrio/química , Oligonucleotídeos/química , Guanina/química , Conformação de Ácido Nucleico , Hibridização de Ácido Nucleico , Termodinâmica , Timina/química
8.
Colloids Surf B Biointerfaces ; 143: 352-358, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-27022876

RESUMO

Biocompatible nanogels were prepared using thiol modified hyaluronic acid and diacrylated pluronic F127 polymer. A simple Michael type addition reaction of activated thiol groups on acrylate moiety lead to the formation of these nanogels, which were further effectively fabricated with an anticancer drug for evaluating sustained drug release approach. Nanogels prepared were of 150nm in diameter with a narrow size distribution pattern. DOX released from these nanogels showed a slow and sustained release at acidic pH 5.0 as compared to minimal release at physiological pH 7.4. Cytotoxicity data revealed the higher efficiency of DOX loaded nanogels as compared to free DOX in Hela cell lines. Cellular uptake images supported the cytotoxicity data and displayed DOX intercalation at nuclear level of cells. The sustained drug delivery system showed DOX release after 24h and continued thereafter without affecting normal cells. Based on these findings, such nanogel system may be useful for delivering anticancer drug without hampering their toxicity value over longer durations and reducing the total dose amount in anticancer therapy.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Preparações de Ação Retardada/síntese química , Doxorrubicina/farmacologia , Portadores de Fármacos/síntese química , Ácido Hialurônico/química , Nanoestruturas/química , Acrilatos/química , Antibióticos Antineoplásicos/química , Sequência de Carboidratos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Portadores de Fármacos/farmacologia , Liberação Controlada de Fármacos , Géis , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Metaloproteinase 2 da Matriz/metabolismo , Polietilenos/química , Polipropilenos/química
9.
PLoS One ; 9(9): e106039, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25216353

RESUMO

Diabetes mellitus is a multifactorial metabolic disease characterized by post-prandial hyperglycemia (PPHG). α-amylase and α-glucosidase inhibitors aim to explore novel therapeutic agents. Herein we report the promises of Dioscorea bulbifera and its bioactive principle, diosgenin as novel α-amylase and α-glucosidase inhibitor. Among petroleum ether, ethyl acetate, methanol and 70% ethanol (v/v) extracts of bulbs of D. bulbifera, ethyl acetate extract showed highest inhibition upto 72.06 ± 0.51% and 82.64 ± 2.32% against α-amylase and α-glucosidase respectively. GC-TOF-MS analysis of ethyl acetate extract indicated presence of high diosgenin content. Diosgenin was isolated and identified by FTIR, 1H NMR and 13C NMR and confirmed by HPLC which showed an α-amylase and α-glucosidase inhibition upto 70.94 ± 1.24% and 81.71 ± 3.39%, respectively. Kinetic studies confirmed the uncompetitive mode of binding of diosgenin to α-amylase indicated by lowering of both Km and Vm. Interaction studies revealed the quenching of intrinsic fluorescence of α-amylase in presence of diosgenin. Similarly, circular dichroism spectrometry showed diminished negative humped peaks at 208 nm and 222 nm. Molecular docking indicated hydrogen bonding between carboxyl group of Asp300, while hydrophobic interactions between Tyr62, Trp58, Trp59, Val163, His305 and Gln63 residues of α-amylase. Diosgenin interacted with two catalytic residues (Asp352 and Glu411) from α-glucosidase. This is the first report of its kind that provides an intense scientific rationale for use of diosgenin as novel drug candidate for type II diabetes mellitus.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/enzimologia , Dioscorea/química , Diosgenina/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo , Animais , Domínio Catalítico , Dicroísmo Circular , Diabetes Mellitus Experimental/patologia , Diosgenina/química , Diosgenina/farmacologia , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Intestinos/enzimologia , Cinética , Camundongos , Simulação de Acoplamento Molecular , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ligação Proteica/efeitos dos fármacos , Espectrometria de Fluorescência , Sus scrofa , alfa-Amilases/metabolismo
10.
PLoS One ; 8(12): e82529, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24367520

RESUMO

Gnidia glauca and Dioscorea bulbifera are traditional medicinal plants that can be considered as sources of natural antioxidants. Herein we report the phytochemical analysis and free radical scavenging activity of their sequential extracts. Phenolic and flavonoid content were determined. Scavenging activity was checked against pulse radiolysis generated ABTS(•+) and OH radical, in addition to DPPH, superoxide and hydroxyl radicals by biochemical methods followed by principal component analysis. G. glauca leaf extracts were rich in phenolic and flavonoid content. Ethyl acetate extract of D. bulbifera bulbs and methanol extract of G. glauca stem exhibited excellent scavenging of pulse radiolysis generated ABTS(•+) radical with a second order rate constant of 2.33 × 10(6) and 1.72 × 10(6), respectively. Similarly, methanol extract of G. glauca flower and ethyl acetate extract of D. bulbifera bulb with second order rate constants of 4.48 × 10(6) and 4.46 × 10(6) were found to be potent scavengers of pulse radiolysis generated OH radical. G. glauca leaf and stem showed excellent reducing activity and free radical scavenging activity. HPTLC fingerprinting, carried out in mobile phase, chloroform: toluene: ethanol (4: 4: 1, v/v) showed presence of florescent compound at 366 nm as well as UV active compound at 254 nm. GC-TOF-MS analysis revealed the predominance of diphenyl sulfone as major compound in G. glauca. Significant levels of n-hexadecanoic acid and octadecanoic acid were also present. Diosgenin (C27H42O3) and diosgenin (3á,25R) acetate were present as major phytoconstituents in the extracts of D. bulbifera. G. glauca and D. bulbifera contain significant amounts of phytochemicals with antioxidative properties that can be exploited as a potential source for herbal remedy for oxidative stress induced diseases. These results rationalize further investigation in the potential discovery of new natural bioactive principles from these two important medicinal plants.


Assuntos
Antioxidantes/química , Dioscorea/química , Depuradores de Radicais Livres/química , Extratos Vegetais/química , Plantas Medicinais/química , Cromatografia Líquida de Alta Pressão , Flavonas/química , Fenol/química , Análise de Componente Principal
11.
ISRN Org Chem ; 2013: 453682, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24052861

RESUMO

A new, efficient method for the synthesis of 2-aryl substituted benzimidazole by using silica supported periodic acid (H5IO6-SiO2) as a catalyst has been developed. The salient feature of the present method includes mild reaction condition, short reaction time, high yield and easy workup procedure. The synthesized benzimidazoles exhibited potent anticancer activity against MCF7 and HL60 cell lines.

12.
Dalton Trans ; 42(5): 1519-29, 2013 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-23135734

RESUMO

Solvent extraction studies of actinide metal ions such as Am(III), U(VI), Np(IV), Np(VI), Pu(IV) were carried out in a nitric acid medium using two diamides (L) viz. (DMDBTDMA (N,N'-dimethyl-N,N'-dibutyl-2-tetradecylmalonamide) and DMDOHEMA (N,N'-dimethyl-N,N'-dioctyl-2-(2'-(hexyloxy)ethyl)-malonamide) dissolved in different room temperature ionic liquids (RTILs). The use of RTILs as the diluent significantly enhanced metal ion extraction as compared to that observed in non polar diluent such as n-dodecane. The effects of parameters such as kinetics, aqueous phase acidity (0.01-3 M HNO(3)), metal ion oxidation states, diamide concentration on the extraction of metal ions were studied. The stoichiometry of the extracted Am(III) species using these diamides varied with ligand concentration viz. (Am.3L)(3+) ([L] = 0.005-0.02 M) and (Am.2-2.5L)(3+) ([L] = 0.05-0.1 M). Time resolved laser induced fluorescence spectroscopy (TRLFS) studies showed that the extracted species of Eu(III) in an ionic liquid medium had no coordinated water molecules, in contrast to the presence of 1-2 water molecules in the extracted species in a n-dodecane medium. The radiolytic degradation behavior of the diamides/RTIL system has been studied using IR spectroscopy and gas chromatography-mass spectrometry (GC-MS). The data revealed that a significantly lower ligand concentration is required for actinide extraction in ionic liquids as the extraction media as compared to nonpolar diluents.

13.
Macromol Biosci ; 11(2): 199-210, 2011 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-21104878

RESUMO

The synthesis and characterization of spherical sugar-containing polymer brushes consisting of PS cores onto which chains of sugar-containing polymers have been grafted via two different techniques are described. Photopolymerization in aqueous dispersion using the functional monomer MAGlc and crosslinked or non-crosslinked PS particles covered with a thin layer of photo-initiator yielded homogeneous glycopolymer brushes attached to spherical PS cores. As an alternative, ATRP was used to graft poly-(N-acetylglucosamine) arms from crosslinked PS cores. Deprotection of the grafted brushes led to water-soluble particles that act as carriers for catalytically active gold nanoparticles. These glycopolymer chains show a high affinity to adsorb WGA whereas no binding to BSA or PNA could be detected.


Assuntos
Carboidratos/química , Carboidratos/síntese química , Nanosferas/química , Poliestirenos/química , Poliestirenos/síntese química , Acetilglucosamina/síntese química , Animais , Catálise/efeitos da radiação , Bovinos , Cromatografia em Gel , Glucose/química , Ouro/química , Hidrodinâmica , Cinética , Luz , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Transmissão , Peso Molecular , Tamanho da Partícula , Polimerização/efeitos da radiação , Espectroscopia de Infravermelho com Transformada de Fourier , Aglutininas do Germe de Trigo/química
14.
Bioorg Med Chem Lett ; 20(24): 7243-5, 2010 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-21074431

RESUMO

New homologues of harzialactone were synthesized using D-glucose as chiral template. Wittig reaction to introduce aromatic moiety in 10 and chemoselective anomeric oxidation of 13 were used as key reactions in our synthesis. Anticancer activity of these target molecules was assessed against five cancer cell lines, P388D1, HL60, COLO-205, Zr-75-1 and HeLa. Both compound 5 and 6, showed significant activity against colon cancer (COLO-205) and cervical cancer (HeLa) and moderate with others. To the best of our knowledge, this is the first report of harzialactone analogues as potent inhibitors of human colon and cervical cancer.


Assuntos
4-Butirolactona/análogos & derivados , Antineoplásicos/síntese química , Lactonas/química , 4-Butirolactona/síntese química , 4-Butirolactona/química , 4-Butirolactona/uso terapêutico , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Glucose/química , Humanos , Lactonas/síntese química , Lactonas/uso terapêutico , Oxirredução , Estereoisomerismo , Relação Estrutura-Atividade , Neoplasias do Colo do Útero/tratamento farmacológico
15.
Bioorg Med Chem ; 18(22): 7799-803, 2010 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-20971014

RESUMO

The first stereoselective synthesis of (2S,3R,6S)-6-methyl-3-hydroxy-piperidine-2-carboxylic acid (-)-6 and (2R,3R,6S)-6-methyl-(2-hydroxymethyl)-piperidine-3-ol (+)-7 was achieved starting from readily available d-glucose in 14 steps with 17% overall yield for both the compounds. The key feature of the present strategy includes the Wittig-olefination for the preparation of required conjugated keto-azide 9 and construction of 2,3,6-trisubstituted piperidine skeleton 11 by applying intramolecular reductive cyclization of conjugated keto-azide intermediate. The glycosidase inhibitory activity of compounds 6 and 7 towards several glycosidases has been evaluated.


Assuntos
Inibidores Enzimáticos/síntese química , Glicosídeo Hidrolases/antagonistas & inibidores , Ácidos Pipecólicos/síntese química , Ciclização , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Geobacillus/enzimologia , Glicosídeo Hidrolases/metabolismo , Oxirredução , Ácidos Pipecólicos/química , Ácidos Pipecólicos/farmacologia , Piperidinas/química , Saccharomyces cerevisiae/enzimologia , Estereoisomerismo
16.
J Org Chem ; 71(12): 4667-70, 2006 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-16749803

RESUMO

The intramolecular aminomercuration reaction of sugar-derived beta-hydroxy-gamma-alkenylamines 8a-c undergoes 5-endo-trig cyclization in high yield. The sugar-substituted pyrrolidines thus obtained were elaborated to the synthesis of polyhydroxylated indolizidine alkaloids, namely, castanospermine 1a, 1-epi-castanospermine 1b, and 8a-epi-castanospermine 1c, having promising glycosidase inhibitory activities.


Assuntos
Indolizinas/síntese química , Pirrolidinas/síntese química , Aminas/química , Ciclização , Glucosidases/antagonistas & inibidores , Mercúrio/química
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