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1.
Antioxidants (Basel) ; 5(4)2016 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-27775557

RESUMO

Various species of berries have been reported to contain several polyphenolic compounds, such as anthocyanins and flavonols, which are known to possess high antioxidant activity and may be beneficial for human health. To our knowledge, a thorough chemical analysis of polyphenolics in species of these plants native to Newfoundland, Canada has not been conducted. The primary objective of this study was to determine the polyphenolic compounds present in commercial extracts from Newfoundland berries, which included blueberries (V. angustifolium), lingonberries (V. vitis-idaea) and black currant (Ribes lacustre). Anthocyanin and flavonol glycosides in powdered extracts from Ribes lacustre and the Vaccinium species were identified using the high performance liquid chromatographic (HPLC) separation method with mass spectrometric (MS) detection. The identified compounds were extracted from dried berries by various solvents via ultrasonication followed by centrifugation. A reverse-phase analytical column was employed to identify the retention time of each chemical component before submission for LC-MS analysis. A total of 21 phenolic compounds were tentatively identified in the three species. Further, we tested the effects of the lingonberry extract for its ability to protect neurons and glia from trauma utilizing an in vitro model of cell injury. Surprisingly, these extracts provided complete protection from cell death in this model. These findings indicate the presence of a wide variety of anthocyanins and flavonols in berries that grow natively in Newfoundland. These powdered extracts maintain these compounds intact despite being processed from berry fruit, indicating their potential use as dietary supplements. In addition, these recent findings and previous data from our lab demonstrate the ability of compounds in berries to protect the nervous system from traumatic insults.

2.
Molecules ; 21(6)2016 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-27338318

RESUMO

Chlorogenic acid is a well known natural product with important bioactivities. It contains an ester bond formed between the COOH of caffeic acid and the 3-OH of quinic acid. We synthesized a chlorogenic acid analogue, 3α-caffeoylquinic acid amide, using caffeic and quinic acids as starting materials. The caffeoylquinc acid amide was found to be much more stable than chlorogenic acid and showed anti-Hepatitis C virus (anti-HCV) activity with a potency similar to chlorogenic acid. The caffeoylquinc acid amide potently protected HepG2 cells against oxidative stress induced by tert-butyl hydroperoxide.


Assuntos
Amidas/química , Antioxidantes/química , Ácido Clorogênico/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Amidas/síntese química , Amidas/uso terapêutico , Antioxidantes/síntese química , Antioxidantes/uso terapêutico , Ácidos Cafeicos/química , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/síntese química , Ácido Clorogênico/química , Ésteres/química , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Humanos , Ácido Quínico/análogos & derivados , Ácido Quínico/química , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo , terc-Butil Hidroperóxido/química
3.
J Pharm Pharm Sci ; 15(1): 52-72, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22365088

RESUMO

Quinolones are considered as a big family of multi-faceted drugs; their chemical synthesis is flexible and can be easily adapted to prepare new congeners with rationally devised structures. This is shown by the description of many thousands of derivatives in the literature. Scientists could accurately describe their QSAR, which is essential for effective drug design. This also gave them the chance to discover new and unprecedented activities, which makes quinolones an endless source of hope and enables further development of new clinically useful drugs. Quinolones are among the most common frameworks present in the bioactive molecules that have dominated the market for more than four decades. Since 1962, 4(1H)-quinolone-3-carboxylic acid derivatives are widely used as antibacterial agents. Quinolones have a broad and potent spectrum of activity and are also used as second-line drugs to treat tuberculosis (TB). Recently, quinolones have been reported to display "nonclassical" biological activities, such as antitumor, anti-HIV-1 integrase, anti-HCV-NS3 helicase and -NS5B-polymerase activities. The present review focuses on the structural modifications responsible for the transformation of an antibacterial into an anticancer agent and/or an antiviral agent. Indeed, quinolones' antimicrobial action is distinguishable among antibacterial agents, because they target different type II topoisomerase enzymes. Many derivatives of this family show high activity against bacterial topoisomerases and eukaryotic topoisomerases, and are also toxic to cultured mammalian cells and in vivo tumor models. Moreover, quinolones have shown antiviral activity against HIV and HCV viruses. In this context the quinolones family of drugs seem to link three different biological activities (antibacterial, anticancer, and the antiviral profiles) and the review will also provide an insight into the different mechanisms responsible for these activities among different species.


Assuntos
Quinolonas/farmacologia , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Inibidores de Integrase de HIV/farmacologia , Quinolonas/química , Fatores de Transcrição STAT/antagonistas & inibidores , Relação Estrutura-Atividade
4.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 2): o529, 2011 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-21523177

RESUMO

In the title mol-ecule, C(16)H(9)NO(5)S, there is an intra-molecular O-H⋯O hydrogen bond involving the quinolone carbonyl O atom and a carboxyl OH group. In the crystal, inter-molecular O-H⋯O hydrogen bonds between the carbonyl group of the quinolone carboxyl group, and a second carboxyl group on the thia-zeto moiety lead to the formation of chains propagating along [201] and perpendicular to the π-stacks of mol-ecules.

5.
Bioorg Med Chem ; 18(19): 7009-14, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20813534

RESUMO

New derivatives of caffeic acid and quinic acid were synthesized and their anti-fungal and inhibitory activities on fungal 1,3-ß-glucan synthase were determined in comparison with those of the corresponding chlorogenic acid derivatives. All the chlorogenic, quinic and caffeic acid derivatives that were coupled with an H(2)N-orn-4-(octyloxy) aniline group (1, 1b and 1c) displayed potent activities in both anti-fungal and inhibition of 1,3-glucan synthase assays. Compounds 1 and 1c inhibited the fungal membrane enzyme with the potency comparable to that of a known 1,3-ß-D-glucan synthase inhibitor, aculeacin A. The results revealed that the anti-fungal activity of the chlorogenic acid derivative with a free amino group was at least partly due to inhibition of the fungal 1,3-ß-glucan synthase. These results suggest that further investigation on caffeic acid derivatives may lead to the discovery of novel anti-fungal agents with drug-like properties.


Assuntos
Antifúngicos/farmacologia , Ácidos Cafeicos/farmacologia , Candida albicans/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Glucosiltransferases/antagonistas & inibidores , Ácido Quínico/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Ácidos Cafeicos/síntese química , Ácidos Cafeicos/química , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Glucosiltransferases/metabolismo , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ácido Quínico/síntese química , Ácido Quínico/química , Estereoisomerismo , Relação Estrutura-Atividade
6.
Bioorg Med Chem ; 18(2): 863-9, 2010 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-20004585

RESUMO

In our continued research on chlorogenic acid analogues and derivatives with improved bioactivity, we have synthesized some caffeoyl 5,6-anhydroquinic acid derivatives. The 1,7 acetonides of chlorogenic acid (15), and of the mono-caffeoyl 5,6-anhydroquinic acids (7-8) showed appreciable anti-HIV activity. The 3,4-dicaffeoyl 5,6-anhydroquinic acid (12) exhibited an anti-HIV activity twice as that of 3,5-dicaffeoylquinic acid (22). The caffeoyl 5,6-anhydroquinic acid derivatives displayed potent anti-oxidant activities. The mono-caffeoyl 5,6-anhydroquinic acids (10-11) were more than twice stronger than chlorogenic acid (21) on SOD-like activity.


Assuntos
Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacologia , Antioxidantes/síntese química , Antioxidantes/farmacologia , Ácidos Cafeicos/síntese química , Ácidos Cafeicos/farmacologia , HIV-1/efeitos dos fármacos , Ácido Quínico/análogos & derivados , Animais , Fármacos Anti-HIV/química , Antioxidantes/química , Ácidos Cafeicos/química , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ácido Quínico/síntese química , Ácido Quínico/química , Ácido Quínico/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade
7.
J Med Chem ; 51(19): 6188-94, 2008 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-18783210

RESUMO

Alpha-glucosidases play important roles in the digestion of carbohydrates and biosynthesis of viral envelope glycoproteins. Inhibitors of alpha-glucosidase are promising candidates for the development of antitype II diabetics and anti-AIDS drugs. Here, we report the synthesis and alpha-glucosidase inhibitory activity of mono- and diketal/acetal derivatives of chlorogenic acid. The diketal derivatives showed more potent inhibitory activity than the monoketals. The 1,7-(5-nonanone) 3,4-(5-nonanone)-chlorogenic acid diketal showed remarkable inhibitory activity against alpha-glucosidases with potency better than that of 1-deoxynojirimycin hydrochloride. Four diasteremers of pelargonaldehyde diacetal and two of monoacetal derivatives of chlorogenic acid were synthesized in this study. They showed significant potent inhibition similar to or more potent than the ketal counterparts. Acetals with the alkyl chain oriented toward position 2 of chlorogenic acid showed more potent activity than those oriented toward position 6.


Assuntos
Alcanos/química , Ácido Clorogênico/síntese química , Ácido Clorogênico/farmacologia , Inibidores Enzimáticos/farmacologia , Inibidores de Glicosídeo Hidrolases , Alquilação , Sítios de Ligação , Ácido Clorogênico/análogos & derivados , Relação Dose-Resposta a Droga , Estabilidade de Medicamentos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Suco Gástrico/química , Geobacillus stearothermophilus/enzimologia , Estrutura Molecular , Saccharomyces cerevisiae/enzimologia , Estereoisomerismo , Relação Estrutura-Atividade
8.
Phytochem Anal ; 19(4): 294-300, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-17994537

RESUMO

An HPLC-PAD-MS(n) method was employed to profile the phenolic compounds of the aerial part of Artemisia pectinata (Neopallasia pectinata), a plant with no previous reports concerning its phenolic constituents. Three isomers of trans-caffeoylquinic acid accompanied by cis-5-caffeoylquinic acid, six isomers of trans-dicaffeoylquinic acid, two isomers of methyl trans-dicaffeoylquinate (including one new isomer), a trans-caffeoylferuloylquinic acid and three flavanoids were identified unambiguously by analysis of their UV and MS(n) spectra in comparison with standard compounds that were isolated from natural sources, or synthesised, or were surrogate standards (green coffee extract). Other compounds were identified by analysis of their UV and MSn data in comparison with those reported in the literature. MS(n) experiments also suggested the presence of groups of dicaffeoylquinic acid glycosides, caffeoylquinic acid diglycosides, caffeoylquinic acid glycosides and quinic acid diglycosides.


Assuntos
Artemisia/química , Cromatografia Líquida de Alta Pressão/métodos , Fenóis/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectroscopia de Ressonância Magnética , Espectrofotometria Ultravioleta
9.
J Pharm Pharm Sci ; 11(2): 44s-55s, 2008 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-19203470

RESUMO

Life-threatening fungal infections have increased dramatically in recent decades in immunocompromised patients. An estimated 40% of all deaths from hospital-acquired infections are due to infections caused by opportunistic fungi. The current treatment options are either causing serious toxicity, or becoming inactive against the drug-resistant fungal strains. Thus, the discovery and development of new antifungal agents that are economically feasible, have excellent therapeutic value, and address the problems of toxicity and species resistance is very important. We have recently designed and synthesized a series of chlorogenic acid-based peptidimimetics using structure-based methodology starting with cyclic peptides of the candin class of antifungals. These novel and totally synthetic compounds exhibit promising antifungal activity against pathogenic fungi with very low toxicity against brine shrimps. The possible novelty in their mechanism of action and economically feasible synthetic approach are the attractive features of this class of compounds that make them different from the already utilized antifungal agents.


Assuntos
Antifúngicos/química , Desenho de Fármacos , Fungos/efeitos dos fármacos , Hospedeiro Imunocomprometido , Peptídeos Cíclicos/química , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Química Farmacêutica , Ácido Clorogênico/química , Indústria Farmacêutica , Humanos , Peso Molecular , Relação Estrutura-Atividade
10.
Bioorg Med Chem ; 15(21): 6830-3, 2007 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-17761420

RESUMO

Derivatives of chlorogenic acid or its analogues were synthesized by coupling protected chlorogenic acid or its analogues with p-octyloxyaniline and selected amino acids. Most of the compounds exhibited significant potency against Cryptococcus neoformans and Candida species with low toxicity to brine shrimps. The 4,5-dihydroxyl groups in the quinic acid moiety were necessary for the activity and introduction of a free amino group increased the inhibitory activity against Aspergillus fumigatus.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Candida/efeitos dos fármacos , Ácido Clorogênico/análogos & derivados , Cryptococcus neoformans/efeitos dos fármacos , Antifúngicos/síntese química
11.
Phytochem Anal ; 18(1): 42-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17260697

RESUMO

A simple HPLC-PAD-MS method was established to quantitatively analyse two spiroether isomers (cis-en-yn-dicycloether and trans-en-yn-dicycloether) and the main coumarin, herniarin, in chamomile herbs, simultaneously. By using this method, the contents of these three compounds in the flowers of two chamomile species, Roman chamomile (Chamaemelum nobile) and pineapple weed (Matricaria matricarioides), as well as in different parts of pineapple weed, were investigated. It was found that the flowers of both herbs contained large amounts of cis-en-yn-dicycloether and trans-en-yn-dicycloether, with the trans-form being more abundant than the cis-form. The leaves of pineapple weed were found to have the highest concentration of cis-en-yn-dicycloether and herniarin than the other parts. HPLC-PAD-MS-guided isolation and identification of other constituents are also discussed.


Assuntos
Chamaemelum/química , Flores/química , Matricaria/química , Umbeliferonas/análise , Calibragem , Cromatografia Líquida de Alta Pressão , Isomerismo , Folhas de Planta/química , Controle de Qualidade , Padrões de Referência , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta , Umbeliferonas/isolamento & purificação
12.
J Mol Graph Model ; 25(4): 459-69, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16621634

RESUMO

Azolylalkylquinolines (AAQs) are a family of quinolines with varying degrees of cytotoxic activity (comparable or moderately superior to adriamycin in some cases) developed in the past decade in our group where their exact mode of action is still unclear. In this study the most probable DNA binding mode of AAQs was investigated employing a novel flexible ligand docking approach by using AutoDock 3.0. Forty-nine AAQs with known experimental inhibitory activity were docked onto d(CGCAAATTTGCG)(2), d(CGATCG)(2) and d(CGCG)(2) oligonucleotides retrieved from the Protein Data Bank (PDB IDs: 102D, 1D12 and 1D32, respectively) as the representatives of the three plausible models of interactions between chemotherapeutic agents and DNA (groove binding, groove binding plus intercalation and bisintercalation, respectively). Good correlation (r(2)=0.64) between calculated binding energies and experimental inhibitory activities was obtained using groove binding plus intercalation model for phenyl-azolylalkylquinoline (PAAQ) series. Our findings show that the most probable mode of action of PAAQs as DNA binding agents is via intercalation of quinolinic moiety between CG base pairs with linker chain and azole moiety binding to the minor groove.


Assuntos
DNA/química , Quinolinas/química , Quinolinas/farmacologia , Sítios de Ligação , Citotoxinas/química , Citotoxinas/metabolismo , Citotoxinas/farmacologia , DNA/efeitos dos fármacos , DNA/metabolismo , Substâncias Intercalantes/química , Substâncias Intercalantes/metabolismo , Substâncias Intercalantes/farmacologia , Ligantes , Modelos Moleculares , Conformação de Ácido Nucleico , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/metabolismo , Oligodesoxirribonucleotídeos/farmacologia , Quinolinas/metabolismo , Software , Termodinâmica
13.
Eur J Med Chem ; 40(6): 582-9, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15922841

RESUMO

Ursolic acid and 2alpha-hydroxyursolic acid isolated from apple peels were found to show growth inhibitory activity against four tumor cell lines, HL-60, BGC, Bel-7402 and Hela. Structural modifications were performed on the C-3, C-28 and C-11 positions of ursolic acid and the cytotoxicity of the derivatives was evaluated. The SAR revealed that the triterpenes possessing two hydrogen-bond forming groups (an H-donor and a carbonyl group) at positions 3 and 28 exhibit cytotoxic activity. The configuration at C-3 was found to be important for the activity. Introduction of an amino group increased the cytotoxicity greatly. A 3beta-amino derivative was 20 times more potent than the parent ursolic acid. The 28-aminoalkyl dimer compounds showed selective cytotoxicity.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Triterpenos/síntese química , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Sobrevivência Celular/efeitos dos fármacos , Feminino , Células HL-60 , Células HeLa , Humanos , Espectroscopia de Ressonância Magnética , Malus/química , Estrutura Molecular , Rodaminas/química , Triterpenos/química
14.
Eur J Med Chem ; 39(8): 699-705, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15276303

RESUMO

Several new and known 2-(4-substituted phenyl)-3(2H)-isothiazolone derivatives with or without chloro substituent at C-5 position were synthesized and their in vitro antibacterial activity against selected Gram-negative and Gram-positive bacteria were evaluated using agar dilution method. Most of compounds exhibited moderate to high activities against tested microorganisms, and in comparison with the reference drugs some compounds showed comparable or higher activities. In contrast to results of the previous studies, some 5-chloro derivatives showed lower or comparable activities against some tested microorganism, in comparison with analogues without C-5 substitution. In general, most of the compounds bearing electron withdrawing group at 4-position of the phenyl ring were more active against Gram-positive and most of those having piperazine derivatives were more active against Gram-negative bacteria.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Tiazóis/síntese química , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Tiazóis/farmacologia
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