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1.
J Org Chem ; 86(7): 5213-5226, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33764066

RESUMO

Organic transformations exclusively in water as an environmentally friendly and safe medium have drawn significant interest in the recent years. Moreover, transition metal-free synthesis of enantiopure molecules in water will have a great deal of attention as the system will mimic the natural enzymatic reactions. In this work, a new set of proline-derived hydrophobic organocatalysts have been synthesized and utilized for asymmetric Michael reactions in water as the sole reaction medium. Among the various catalysts screened, the catalyst 1 is indeed efficient for stereoselective 1,4-conjugated Michael additions (dr: >97:3, ee up to >99.9%) resulting in high chemical yields (up to 95%) in a very short reaction time (1 h) at room temperature. This methodology provides a robust, green, and convenient protocol and can thus be an important addition to the arsenal of the asymmetric Michael addition reaction. Upon successful implementation, the present strategy also led to the formation of an optically active octahydroindole, the key component found in many natural products.

2.
J Org Chem ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710890

RESUMO

A p-TsOH-mediated one-pot, three-component methodology has been developed for the synthesis of pyrrolo/indolo[1,2-a]quinoxalines substituted with o-biphenylester/N-arylcarbamate/N-arylurea at the C-4 position under open-air heating conditions. The protocol offers a transition-metal-free and external oxidant-free solvent-mediated pathway to afford a library of diversely substituted quinoxalines in moderate to good yields. Various water-miscible aliphatic alcohols and amines participate in the reactions both as solvent as well as reactant. X-ray crystal structure analysis suggests that some of the suitably substituted quinoxalines may exhibit atropisomerism at room temperature.

3.
Bioorg Chem ; 98: 103734, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32171990

RESUMO

Diminution of oxidative stress-mediated diseases is an essential pharmaceutical objective in modern biomedical research. The present work stresses upon the efficient and eco-friendly synthesis of an array of novel diversely functionalized pyrrole derivatives which are found to be antioxidants with reactive oxygen species (ROS) shielding competency against the deleterious consequence of oxidative stress. The results of the investigation displayed the effect of structural modification of the pyrrole derivatives on their respective antioxidant properties to various ROS. Noteworthy, the pyrrole moiety bearing 4-hydroxycoumarin or 2-hydroxy-1,4-naphthoquinone as substituent showed outstanding defensive potency towards OH and O2- while, nitrogen atom linked with aliphatic side-chain in the pyrrole scaffold made a strong affirmative impression in DPPH scavenging assay. More interestingly, an influencing reducing power was observed in pyrrole derivatives carrying cyclohexane 1,3-dione as one of the substituents. To have a comprehensive acuteness into the antioxidant capacity of the synthesized pyrrole derivatives against Trolox as a standard antioxidant, a crucial approach was taken into account by calculating TEAC (Trolox Equivalent Antioxidant Capacity) in case of OH and DPPH scavenging activity.

4.
J Med Chem ; 62(13): 6315-6329, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31246452

RESUMO

Reduction of mitochondrial oxidative stress-mediated diseases is an important pharmaceutical objective in recent biomedical research. In this context, a series of novel pyrrolobenzoxazines (PyBs) framework with enormous diversity (compounds 5a-w) was synthesized by employing a low-temperature greener pathway, and antioxidant property of the synthesized compounds was successfully demonstrated on preclinical model goat heart mitochondria, in vitro. Copper-ascorbate (Cu-As) was utilized as an oxidative stress generator. Out of screened PyBs, the compound possessing -OH and -OMe groups on benzene nucleus along with pyrrolobenzoxazine core moiety (compound 5w) displayed magnificent antioxidant property with a minimum effective dose of 66 µM during the biochemical assessment. The ameliorative effect of synthesized pyrrolobenzoxazine moiety on levels of biomarkers of oxidative stress, antioxidant enzyme, activities of Krebs cycle and respiratory chain enzymes, mitochondrial morphology, and Ca2+ permeability of mitochondrial membrane was investigated in the presence of Cu-As. Furthermore, the binding mode of Cu-As by compound 5w was explored successfully using isothermal titration calorimetry (ITC) analysis.


Assuntos
Benzoxazinas/farmacologia , Depuradores de Radicais Livres/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Pirróis/farmacologia , Animais , Ácido Ascórbico/farmacologia , Benzoxazinas/síntese química , Biomarcadores/metabolismo , Ciclo do Ácido Cítrico/efeitos dos fármacos , Cobre/farmacologia , Depuradores de Radicais Livres/síntese química , Glutationa/metabolismo , Cabras , Peroxidação de Lipídeos/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Membranas Mitocondriais/metabolismo , Carbonilação Proteica/efeitos dos fármacos , Pirróis/síntese química , Superóxido Dismutase/metabolismo
5.
J Org Chem ; 84(11): 7265-7278, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31074279

RESUMO

A one-pot, three-component, transition-metal-free regioselective sulfenylation of 2-iminothiazoline through the cross-dehydrogenative coupling strategy via sp2 C-H functionalization has been developed employing iodine as a catalyst and dimethyl sulfoxide as an oxidant. Utility of this sulfenylation technique has been well depicted through participation of various aryl and heterocyclic thiols. Significant features of this C-H functionalization strategy include metal-free open air reaction conditions, which offer a mild and efficient method for sulfenylation to achieve diversely substituted 5-sulfenyl-2-iminothiazoline derivatives.

6.
Anal Bioanal Chem ; 411(6): 1143-1157, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30627799

RESUMO

A novel rhodamine-tryptamine conjugate-based fluorescent and chromogenic chemosensor (RTS) for detection of Hg2+ present in water was reported. After gradual addition of Hg2+ in aqueous methanol solution of RTS, a strong orange fluorescence and deep-pink coloration were observed. The probe showed high selectivity towards Hg2+ compared to other competitive metal ions. The 1:1 binding stoichiometry between RTS and Hg2+ was established by Job's plot analysis and mass spectroscopy. Initial studies showed that the synthesized probe RTS possessed fair non-toxicity and effectively passed through cell walls of model cell systems, viz., human neuroblastoma (SHSY5Y) cells and cervical cells (HeLa) to detect intercellular Hg2+ ions, signifying its utility in biological system. The limit of detection (LOD) was found to be 2.1 nM or 0.42 ppb by fluorescence titration. Additionally, the potential relevance of synthesized chemosensor for detecting Hg2+ ions in environmental water samples has been demonstrated. Graphical abstract ᅟ.


Assuntos
Corantes Fluorescentes/química , Mercúrio/análise , Imagem Óptica/métodos , Rodaminas/química , Triptaminas/química , Linhagem Celular Tumoral , Monitoramento Ambiental/métodos , Humanos , Limite de Detecção , Microscopia Confocal/métodos , Espectrometria de Fluorescência/métodos , Poluentes Químicos da Água/análise
7.
J Org Chem ; 84(2): 1053-1063, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30577689

RESUMO

Pyrrolidine-oxadiazolone based organocatalysts are envisaged, synthesized, and utilized for asymmetric Michael reactions. Results of the investigations suggest that some of the catalysts are indeed efficient for stereoselective 1,4-conjugated Michael additions (dr: >97:3, ee up to 99%) in high chemical yields (up to 97%) often in short reaction time. As an extension, one enantiopure Michael adduct has been utilized to synthesize optically active octahydroindole.

8.
Mol Divers ; 21(1): 89-100, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27677738

RESUMO

A one-pot three-component protocol has been developed for the synthesis of amino ester-embedded benzimidazoles under metal-free neutral conditions. Sequentially, the methodology involves coupling of an amino ester with 1-fluoro-2-nitrobenzene, reduction of the coupled nitroarene by sodium dithionite, and cyclization of the corresponding diamine with an aldehyde.


Assuntos
Benzimidazóis/química , Benzimidazóis/síntese química , Ésteres/química , Técnicas de Química Sintética
9.
Mol Divers ; 20(3): 619-26, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26829938

RESUMO

A simple and efficient one-pot methodology has been developed for the synthesis of biologically important multi-functionalized 3-(2[Formula: see text]-hydroxyaryl)-2-(2[Formula: see text]-carboxyphenyl)benzofurans using silica sulfuric acid (SSA) as a heterogeneous acid catalyst in DMF medium. The significant advantages of this methodology are the use of SSA as a recyclable solid acid catalyst, operational simplicity, easy availability of the starting materials, and good yield of the products with high atom-economy.


Assuntos
Benzofuranos/síntese química , Ninidrina/química , Fenóis/química , Dióxido de Silício/química , Benzofuranos/química , Catálise , Técnicas de Química Sintética , Estrutura Molecular , Ácidos Sulfúricos/química
10.
J Phys Chem B ; 119(31): 10114-23, 2015 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-26147185

RESUMO

The proton transfer (PT) process in 1-(2-hydroxy-5-chloro-phenyl)-3,5-dioxo-1H-imidazo-[3,4-b]isoindole (ADCL) has been studied in three different copolymer-surfactant supramolecular assemblies prepared in aqueous 1% P123 triblock copolymer micellar solution with varying concentrations of surfactants (sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), and triton-X-100 (TX 100)). The aim of the present study is to monitor the modulation of the PT process by changing the degree of micellar hydration inside the P123 micelle with the addition of the three different surfactants (two ionic and one non ionic), that is, in P123-surfactant aggregates. Besides, a comparative study has been done with these results with those in water, pure P123 micellar medium and three different surfactants medium. The micropolarity measurement and time-resolved fluorescence anisotropic measurements have been performed to evaluate the binding location of the probe (ADCL) in the three different copolymer-surfactant supramolecular assemblies. It is found that the micropolarity at the binding site of the molecule in the various environments largely influences the PT rate of ADCL. The PT rate is found to be the slowest in the P123 medium and in P123-surfactant aggregates the rate becomes faster as the micropolarity around the binding locations of the molecule in these aggregates is higher in comparison to that in P123 micelle.


Assuntos
Imidazóis/química , Isoindóis/química , Polímeros/química , Prótons , Tensoativos/química , Micelas , Modelos Moleculares , Estrutura Molecular
11.
Mol Divers ; 19(3): 459-71, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25802173

RESUMO

A convenient protocol for the library synthesis of biologically important 1-aryl-2',6-spiro(1',3'-indanedione)-1H-indeno[1,2-b]quinoline-5,7-diones has been developed. In this one-pot reaction protocol a tetrone is condensed with various N-aryl/alkylenamines of 1,3-cyclohexadiones on the surface of a solid-supported acid catalyst silica sulfuric acid under solvent-free condition. The significant advantages of this methodology are the use of solvent-free reaction conditions, operational simplicity of the reaction, good yield of the products with high atom economy, and employment of a recyclable catalyst. All these favorable factors make the present method convenient, economic, and 'benign by design'.


Assuntos
Aminas/química , Di-Hidropiridinas/química , Indanos/química , Dióxido de Silício/química , Compostos de Espiro/química , Compostos de Espiro/síntese química , Ácidos Sulfúricos/química , Catálise , Técnicas de Química Sintética , Solventes/química
12.
J Phys Chem B ; 119(6): 2168-79, 2015 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-25068392

RESUMO

This article describes the interaction of a micelle entrapped pharmaceutically important isoindole fused imidazole derivative, namely, 1-(2-hydroxy-5-methyl-phenyl)-3,5-dioxo-1H-imidazo-[3,4-b] isoindole (ADII), with the model transport protein bovine serum albumin (BSA). Different spectroscopic techniques such as steady state absorption, emission, circular dichroism, dynamic light scattering, etc., have been employed to explore preferential interaction of this drug template with micelles and protein BSA. Binding of ADII with BSA is found to be enormously modified when it is released from the micellar environment. The binding constant of the ADII-BSA complex is reduced when the probe is released from anionic SDS micelle, whereas the binding is observed to be strengthened in cationic CTAB micellar medium due to the formation of a 1:2 complex (ADII-BSA). Time-resolved studies also support our steady state findings that the released drug from the micellar environment is found to be strongly bound with the protein BSA. Circular dichroism (CD) and dynamic light scattering (DLS) study reveals that the secondary structure of BSA gets some stabilization in SDS medium after binding of drug template to protein. The probable binding location of the probe within the protein cavity (hydrophilic subdomain IA) has been explored from an AutoDock-based blind docking simulation study.


Assuntos
Imidazóis/química , Indóis/química , Isoindóis/química , Micelas , Prótons , Soroalbumina Bovina/química , Animais , Tampões (Química) , Bovinos , Cetrimônio , Compostos de Cetrimônio/química , Lactamas/química , Simulação de Acoplamento Molecular , Octoxinol/química , Ligação Proteica , Conformação Proteica , Dodecilsulfato de Sódio/química , Tensoativos/química , Água/química
13.
Beilstein J Org Chem ; 9: 2344-53, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24367398

RESUMO

A convenient and efficient methodology for the synthesis of densely substituted pyrrole-fused isocoumarins, which employs solid-supported silica sulfuric acid (SSA) as catalyst, has been developed. When the mixture of ninhydrin adducts of acetylacetone/ethyl acetoacetate and primary amines was heated on the solid surface of SSA under solvent-free conditions, the pyrrole-fused isocoumarins were formed in good yields. This synthetic method has several advantages such as the employment of solvent-free reaction conditions without the use of any toxic reagents and metal catalysts, the ease of product isolation, the use of a recyclable catalyst, the low cost, the easy availability of the starting materials, and the excellent yields of products.

14.
Small ; 8(7): 984-90, 2012 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-22323423

RESUMO

An opioid (leucine-enkephalin) conformational analogue forms diverse nanostructures such as vesicles, tubes, and organogels through self-assembly. The nanovesicles encapsulate the natural hydrophobic drug curcumin and allow the controlled release through cation-generated porogens in membrane mimetic solvent.


Assuntos
Encefalina Leucina/química , Nanoestruturas/química , Nanotecnologia/métodos , Curcumina/administração & dosagem , Curcumina/química , Portadores de Fármacos/química , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Nanoestruturas/ultraestrutura
15.
J Nanosci Nanotechnol ; 11(8): 6747-56, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22103076

RESUMO

A set of backbone modified peptides of general formula Boc-Xx-m-ABA-Yy-OMe where m-ABA is meta-aminobenzoic acid and Xx and Yy are natural amino acids such as Phe, Gly, Pro, Leu, Ile, Tyr and Trp etc., are found to self-assemble into soft nanovesicular structures in methanol-water solution (9:1 by v/v). At higher concentration the peptides generate larger vesicles which are formed through fusion of smaller vesicles. The formation of vesicles has been facilitated through the participation of various noncovalent interactions such as aromatic pi-stacking, hydrogen bonding and hydrophobic interactions. Model study indicates that the pi-stacking induced self-assembly, mediated by m-ABA is essential for well structured vesicles formation. The presence of conformationally rigid m-ABA in the backbone of the peptides also helps to form vesicular structures by restricting the conformational entropy. The vesicular structures get disrupted in presence of various salts such as KCI, CaCl2, N(n-Bu)4Br and (NH4)2SO4 in methanol-water solution. Fluorescence microscopy and UV studies reveal that the soft nanovesicles encapsulate organic dye molecules such as Rhodamine B and Acridine Orange which could be released through salts induced disruption of vesicles.


Assuntos
Nanoestruturas , Oligopeptídeos/química , Sais/química , Cristalografia por Raios X , Microscopia de Força Atômica , Microscopia Eletrônica/métodos , Microscopia de Fluorescência , Modelos Moleculares , Espectrofotometria Infravermelho , Termogravimetria
16.
Protein Pept Lett ; 18(9): 886-97, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21443496

RESUMO

In the biomimetic design two hydrophobic pentapetides Boc-Ile-Aib-Leu-Phe-Ala-OMe (I) and Boc-Gly-Ile-Aib-Leu-Phe-OMe (II) (Aib: α-aminoisobutyric acid) containing one Aib each are found to undergo solvent assisted self-assembly in methanol/water to form vesicular structures, which can be disrupted by simple addition of acid. The nanovesicles are found to encapsulate dye molecules that can be released by the addition of acid as confirmed by fluorescence microscopy and UV studies. The influence of solvent polarity on the morphology of the materials generated from the peptides has been examined systematically, and shows that fibrillar structures are formed in less polar chloroform/petroleum ether mixture and vesicular structures are formed in more polar methanol/water. Single crystal X-ray diffraction studies reveal that while ß-sheet mediated self-assembly leads to the formation of fibrillar structures, the solvated ß-sheet structure leads to the formation of vesicular structures. The results demonstrate that even hydrophobic peptides can generate vesicular structures from polar solvent which may be employed in model studies of complex biological phenomena.


Assuntos
Ácidos Aminoisobutíricos/química , Materiais Biomiméticos/química , Corantes/administração & dosagem , Oligopeptídeos/química , Sequência de Aminoácidos , Cristalografia por Raios X , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Estrutura Secundária de Proteína , Solventes
17.
Chem Biodivers ; 7(2): 363-75, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20151383

RESUMO

Three structurally different types of small peptides, namely, i) Boc-Ile-Aib-Ile-OMe (Aib=alpha-aminoisobutyric acid), ii) Boc-Xx-m-aminobenzoic acid (Xx=beta-Ala and gamma-aminobutyric acid), and iii) Boc-Xx-m-nitroaniline, were found to exhibit beta-sheet-mediated fibrillogenesis in the solid state, revealed by FT-IR, single-crystal X-ray diffraction, and FE-SEM studies. Interestingly, the fibrils grown from peptides 2 and 3 were found to bind with the physiological dye Congo red, a characteristic feature of amyloid fibrils.


Assuntos
Amiloide/química , Peptídeos/química , Vermelho Congo/química , Cristalografia por Raios X , Modelos Moleculares , Conformação Molecular , Peptídeos/síntese química , Estrutura Secundária de Proteína
18.
Protein Pept Lett ; 16(9): 1063-73, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19508219

RESUMO

Single crystal X-ray diffraction studies and solvent dependent (1)H NMR titrations reveal that a set of four tetrapeptides with general formula Boc-Xx(1)-Aib(2)-Yy(3)-Zz(4)-OMe, where Xx, Yy and Zz are coded L-amino acids, adopt equivalent conformations that can be described as overlapping double turn conformations stabilized by two 4-->1 intramolecular hydrogen bonds between Yy(3)-NH and Boc C=O and Zz(4)-NH and Xx(1)C=O. In the crystalline state, the double turn structures are packed in head-to-tail fashion through intermolecular hydrogen bonds to create supramolecular helical structures. Field emission scanning electron microscopic (FE-SEM) images of the tetrapeptides in the solid state reveal that they can form flat tape-like structures. The results establish that synthetic Aib containing supramolecular helices can form highly ordered self-aggregated amyloid plaque like human amylin.


Assuntos
Ácidos Aminoisobutíricos/química , Oligopeptídeos/química , Amiloide/química , Cristalização , Cristalografia por Raios X , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Microscopia Eletrônica de Varredura , Ressonância Magnética Nuclear Biomolecular , Conformação Proteica , Estrutura Secundária de Proteína
19.
Org Lett ; 8(19): 4263-6, 2006 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-16956202

RESUMO

A new class of heterocycles of isoindole fused imidazoles with phenolic subunits has been readily synthesized by a two-step one-pot reaction. In aprotic solvent they show high fluorescent properties (Phi(F) up to 0.93), but in protic polar solvent fluorescent intensity decreases. They show green fluorescence in weak acidic medium such as acetic acid but lack emission in basic medium. The compounds can also stain human squamous epithelium cells.


Assuntos
Compostos Heterocíclicos/síntese química , Imidazóis/síntese química , Indóis/química , Fenóis/química , Cristalografia por Raios X , Ligação de Hidrogênio , Imidazóis/química , Espectrometria de Fluorescência
20.
Org Biomol Chem ; 3(12): 2250-4, 2005 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-16010358

RESUMO

Single crystal X-ray diffraction studies show that the extended structure of dipeptide Boc-beta-Ala-m-ABA-OMe (m-ABA: meta-aminobenzoic acid) self-assembles in the solid state by intermolecular hydrogen bonding to create an infinite parallel beta-sheet structure. In dipeptide Boc-gamma-Abu-m-ABA-OMe (gamma-Abu: gamma-aminobutyric acid), two such parallel beta-sheets are further cross-linked by intermolecular hydrogen bonding through m-aminobenzoic acid moieties. SEM (scanning electron microscopy) studies reveal that both the peptides and form amyloid-like fibrils in the solid state. The fibrils are also found to be stained readily by Congo red, a characteristic feature of the amyloid fiber whose accumulation causes several fatal diseases such as Alzheimer's, prion-protein etc.


Assuntos
Aminoácidos/química , Dipeptídeos/química , Ligação de Hidrogênio , Modelos Moleculares , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Espectrofotometria Infravermelho
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