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1.
Alkaloids Chem Biol ; 83: 1-112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32098648

RESUMO

Lamellarins are marine alkaloids containing fused 14-phenyl-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinoline or non-fused 3,4-diarylpyrrole-2-carboxylate ring systems. To date, more than 50 lamellarins have been isolated from a variety of marine organisms, such as mollusks, tunicates, and sponges. Many of them, especially fused type I lamellarins, exhibit impressive biological activity, such as potent cytotoxicity, topoisomerase I inhibition, protein kinases inhibition, and anti-HIV-1 activity. Due to their useful biological activity and limited availability from natural sources, a number of synthetic methods have been developed. In this chapter, we present an updated and comprehensive review on lamellarin alkaloids summarizing their isolation, synthesis, and biological activity.


Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Fármacos Anti-HIV/farmacologia , Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirróis/isolamento & purificação , Pirróis/farmacologia , Inibidores da Topoisomerase I/farmacologia , Alcaloides/síntese química , Alcaloides/química , Animais , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Humanos , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/isolamento & purificação , Pirróis/síntese química , Pirróis/química , Inibidores da Topoisomerase I/síntese química , Inibidores da Topoisomerase I/química , Inibidores da Topoisomerase I/isolamento & purificação
2.
Nat Prod Res ; 34(9): 1197-1205, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30618287

RESUMO

Two new compounds, 5-[2-hydroxypropane-1-yl]-2,6-dimethlbenzene-1,3-diol (1) and coniochaetone L (2), together with 19 known compounds (3-21), were isolated from a deep-sea fungus, Penicillium sp. SCSIO 06720. Their structures and absolute configurations were elucidated by detailed NMR, MS spectroscopic analyses, chiral-phase HPLC analysis, and electronic circular dichroism spectra. All the isolated compounds (1-21) were tested for their antibacterial and HIV latency-reversal activities. Among these compounds, compound 16 showed moderate antibacterial activities against Staphylococcus aureus ATCC 29213 and Methicillin-Resistant Staphylococcus Aureus-shh-1 with MIC values of 10.4 ± 3.7 µg/mL and 46.9 ± 29.7 µg/mL, respectively, which were comparable to that of the positive control ampicillin with MIC values of 0.5 ± 0.4 µg/mL and 2.7 ± 0.9 µg/mL, respectively.


Assuntos
Antibacterianos/isolamento & purificação , Fármacos Anti-HIV/isolamento & purificação , Penicillium/química , Policetídeos/isolamento & purificação , Antibacterianos/química , Antibacterianos/farmacologia , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Policetídeos/química , Policetídeos/farmacologia , Staphylococcus aureus/efeitos dos fármacos
3.
Org Lett ; 22(1): 11-15, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31680527

RESUMO

Three novel gnidimacrin related macrocyclic daphnanes (GMDs), daphneodorins A-C (2-4), were isolated from Daphne odora Thunb., together with gnidimacrin (1). Their structures were established by extensive physicochemical and spectroscopic analyses. Compounds 2 and 3 potently inhibited HIV-1 replication at subnanomolar concentrations (EC50 0.16 and 0.25 nM, respectively). Compounds 2-4 represent a novel type of GMDs that are highly oxygenated on the macrocyclic ring, suggesting good potential for anti-HIV drug development by further chemical modification.


Assuntos
Fármacos Anti-HIV/farmacologia , Daphne/química , HIV-1/efeitos dos fármacos , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Relação Dose-Resposta a Droga , Compostos Macrocíclicos/química , Compostos Macrocíclicos/isolamento & purificação , Compostos Macrocíclicos/farmacologia , Testes de Sensibilidade Microbiana , Conformação Molecular , Relação Estrutura-Atividade , Replicação Viral/efeitos dos fármacos
4.
Phytochemistry ; 170: 112215, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31812106

RESUMO

Acyclotides are plant-based, acyclic miniproteins with cystine knot motif formed by three conserved disulfide linkages and lack head to tail ligation. Acyclotides may not necessarily be less stable, even though they lack cyclic backbone, as the conserved cystine knot feature provides the required stability. Violacin A was the first acyclotide, isolated from Viola odorata in 2006. Until now, acyclotides have been reported from five dicot families (Violaceae, Rubiaceae, Cucurbitaceae, Solanaceae, Fabaceae) and one monocot family (Poaceae). In Poaceae, only acyclotides have been found whereas in dicot families both cyclotides and acyclotides have been isolated. In last 15 years, several acyclotides with antimicrobial, cytotoxic and hemolytic bioactivities have been discovered. Thus, although many naturally expressed acyclotides do exhibit bioactivities, the linearization of the cyclic peptides may result in loss of bioactivities. Although, bioactivities of acyclotides are comparable to their cyclic counterparts, the numbers of isolated acyclotides are still few. Further, those discovered, have the scope to be screened for agriculturally important activities (insecticidal, anti-helminthic, molluscicidal) and pharmaceutical properties (anticancer, anti-HIV, immuno-stimulant). The feasibility of application of acyclotides is because of their relatively less complex biological synthesis compared to cyclotides, as the cyclization step is not needed. This attribute facilitates the production of transgenic crops and/or its expression in heterologous organisms, lacking cyclization machinery. Keeping in view the bioactivities and the wide array of emerging potential applications of acyclotides, the present review discusses their distribution in plants, gene and protein structure, biosynthesis, bioactivities and mechanism of action. Further, their potential applications and future perspectives to exploit them in agriculture and pharmaceutical industries have been highlighted.


Assuntos
Adjuvantes Imunológicos/farmacologia , Fármacos Anti-HIV/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Ciclotídeos/farmacologia , Inseticidas/farmacologia , Compostos Fitoquímicos/farmacologia , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/isolamento & purificação , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Ciclotídeos/química , Ciclotídeos/isolamento & purificação , Humanos , Inseticidas/química , Inseticidas/isolamento & purificação , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
5.
Chin J Nat Med ; 17(12): 945-952, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31882050

RESUMO

Twenty-one lignans including three new ones (1, 2 and 13) were isolated from Justicia procumbens. The chemical structures of the new lignans were determined by spectroscopic means including 1D and 2D NMR analysis. These compounds were evaluated for their cytotoxic and anti-HIV activities. The new secoisolariciresinol dimethyl ether acetate (13) exhibited anti-HIV-1 activity with an IC50 value of 5.27 µmol·L-1 and a selective index (SI) value of 2.2. The known arylnaphthalene lignan procumbenoside A (3) and diphyllin (8) demonstrated inhibitory activity against HIV-1 with IC50 values of 4.95 (SI > 6.2) and 0.38 µmol·L-1 (SI = 5.3), respectively.


Assuntos
Fármacos Anti-HIV/química , HIV-1/efeitos dos fármacos , Adhatoda/química , Lignanas/química , Extratos Vegetais/química , Fármacos Anti-HIV/isolamento & purificação , China , Cromatografia Líquida de Alta Pressão , Lignanas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Componentes Aéreos da Planta/química
6.
Sci Rep ; 9(1): 17076, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745222

RESUMO

Shortly after entering the cell, HIV-1 copies its genomic RNA into double-stranded DNA in a process known as reverse transcription. This process starts inside a core consisting of an enclosed lattice of capsid proteins that protect the viral RNA from cytosolic sensors and degradation pathways. To accomplish reverse transcription and integrate cDNA into the host cell genome, the capsid shell needs to be disassembled, or uncoated. Premature or delayed uncoating attenuates reverse transcription and blocks HIV-1 infectivity. Small molecules that bind to the capsid lattice of the HIV-1 core and either destabilize or stabilize its structure could thus function as effective HIV-1 inhibitors. To screen for such compounds, we modified our recently developed FAITH assay to allow direct assessment of the stability of in vitro preassembled HIV-1 capsid-nucleocapsid (CANC) tubular particles. This new assay is a high-throughput fluorescence method based on measuring the amount of nucleic acid released from CANC complexes under disassembly conditions. The amount of disassembled CANC particles and released nucleic acid is proportional to the fluorescence signal, from which the relative percentage of CANC stability can be calculated. We consider our assay a potentially powerful tool for in vitro screening for compounds that alter HIV disassembly.


Assuntos
Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Nucleocapsídeo/análise , Proteínas do Core Viral/química , Desenvelopamento do Vírus/genética , Sequência de Aminoácidos , Fármacos Anti-HIV/isolamento & purificação , Sequência de Bases , HIV-1/efeitos dos fármacos , Ensaios de Triagem em Larga Escala , Humanos , Nucleocapsídeo/efeitos dos fármacos , RNA Viral/genética , Proteínas do Core Viral/genética , Proteínas do Core Viral/metabolismo , Desenvelopamento do Vírus/efeitos dos fármacos
7.
Fitoterapia ; 139: 104388, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31655087

RESUMO

A new lignan, thoreliin A (1), and a new bisnorlignan, thoreliin B (2), were isolated from a MeOH extract of the rhizomes of Boesenbergia thorelii. In addition, the known bisnorlignans 3 and 4, neolignan 5, phenylpropanoids 6-15, as well as benzenoids 18-21 were also obtained from the same source. The structures were elucidated based on their spectroscopic data. By single crystal X-ray analysis, the relative stereochemistry of 1 was confirmed. All isolated compounds were evaluated for anti-HIV-1 activities. Among them, thoreliin A (1) exhibited anti-HIV-1 activities on both HIV-1 reverse transcriptase (41.43% inhibition at 200 µg/mL) and syncytium reduction assays (EC50 20.6 µM, SI 3.7), while compounds 3-6, 9 and 11-21 showed anti-HIV-1 activity only in the anti-syncytium assay (EC50 6.6-454.1 µM, SI >1.32-7.75).


Assuntos
Fármacos Anti-HIV/farmacologia , HIV-1/efeitos dos fármacos , Lignanas/farmacologia , Rizoma/química , Zingiberaceae/química , Fármacos Anti-HIV/isolamento & purificação , Lignanas/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Tailândia
8.
J Agric Food Chem ; 67(43): 11942-11947, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31622090

RESUMO

Manilkara zapota, usually known as Sapodilla, is a fairly slow-growing evergreen tropical tree which belongs to the genus Manilkara (Sapotaceae), indigenous to Central America, southern Mexico, and the Caribbean. The ripe fruits of M. zapota have been widely consumed as an uniquely flavored tropical fruit and verified to hold a variety of health benefits. In order to investigate the potential health-promoting chemical compositions from the fruits of M. zapota cultivated in Hainan Island of China, a systematic and in-depth phytochemical study on this fruit was accordingly implemented. In our current study, three new prenylated coumarins, manizapotins A-C (1-3), together with seven known prenylated coumarins (4-10), were separated from the fruits of M. zapota. The chemical structures of new prenylated coumarins 1-3 were unambiguously established by means of comprehensive spectroscopic analyses, and the known compounds 4-10 were determined by comparing their experimental spectral data with those described data in the literature. This is the first time to discover prenylated coumarins occurring in M. zapota. The potential anti-inflammatory effects and anti-HIV (human immunodeficiency virus) activities of all these separated prenylated coumarins were assessed. Prenylated coumarins 1-10 dispalyed remarkable inhibitory effects against nitric oxide production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells with the IC50 values equivalent to that of hydrocortisone in vitro. Meanwhile, prenylated coumarins 1-10 exhibited pronounced anti-HIV-1 reverse transcriptase activities with the EC50 values in range of 0.12-8.69 µM. These results suggest that appropriate and reasonable consumption of the fruits of M. zapota might assist people to prevent and reduce the occurrence of inflammatory diseases together with the infection of HIV. Furthermore, the discovery of these prenylated coumarins from the fruits of M. zapota holding pronounced anti-inflammatory effects along with anti-HIV activities could be of great significance to the research and development of new natural anti-inflammatory and anti-HIV agents.


Assuntos
Fármacos Anti-HIV/química , Anti-Inflamatórios/química , Cumarínicos/química , Manilkara/química , Extratos Vegetais/química , Animais , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , China , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Frutas/química , Transcriptase Reversa do HIV/antagonistas & inibidores , Transcriptase Reversa do HIV/metabolismo , HIV-1/efeitos dos fármacos , HIV-1/enzimologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Prenilação , Células RAW 264.7
9.
Mar Drugs ; 17(9)2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31450557

RESUMO

In this study, we aimed to find chemicals from lower sea animals with defensive effects against human immunodeficiency virus type 1 (HIV-1). A library of marine natural products consisting of 80 compounds was screened for activity against HIV-1 infection using a luciferase-encoding HIV-1 vector. We identified five compounds that decreased luciferase activity in the vector-inoculated cells. In particular, portimine, isolated from the benthic dinoflagellate Vulcanodinium rugosum, exhibited significant anti-HIV-1 activity. Portimine inhibited viral infection with an 50% inhibitory concentration (IC50) value of 4.1 nM and had no cytotoxic effect on the host cells at concentrations less than 200 nM. Portimine also inhibited vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped HIV-1 vector infection. This result suggested that portimine mainly targeted HIV-1 Gag or Pol protein. To analyse which replication steps portimine affects, luciferase sequences were amplified by semi-quantitative PCR in total DNA. This analysis revealed that portimine inhibits HIV-1 vector infection before or at the reverse transcription step. Portimine has also been shown to have a direct effect on reverse transcriptase using an in vitro reverse transcriptase assay. Portimine efficiently inhibited HIV-1 replication and is a potent lead compound for developing novel therapeutic drugs against HIV-1-induced diseases.


Assuntos
Fármacos Anti-HIV/farmacologia , Organismos Aquáticos/química , Dinoflagelados/química , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Iminas/farmacologia , Compostos de Espiro/farmacologia , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Células HEK293 , HIV-1/fisiologia , Células HeLa , Humanos , Iminas/isolamento & purificação , Iminas/uso terapêutico , Concentração Inibidora 50 , Compostos de Espiro/isolamento & purificação , Compostos de Espiro/uso terapêutico , Replicação Viral/efeitos dos fármacos
10.
J Nat Prod ; 82(6): 1587-1592, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31184480

RESUMO

Two new (1 and 2) and 14 known (3-16) ingenane diterpenoids were isolated from the roots of Euphorbia ebracteolata by bioassay-guided fractionation together with UPLC-MS n analysis. The absolute configurations of the new diterpenoids were established from electronic circular dichroism (ECD) data and ECD calculations. Except for ingenol (16), the ingenane diterpenoids with long aliphatic chain substituents (1-15) exhibited potent activities against HIV-1, with IC50 values of 0.7 to 9.7 nM and selectivity index values of 96.2 to 20 263. From the results, it was concluded that long aliphatic chain substituents are required for the enhanced anti-HIV activity of ingenane diterpenoids.


Assuntos
Fármacos Anti-HIV/farmacologia , Diterpenos/farmacologia , Euphorbia/química , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Cromatografia Líquida , Diterpenos/química , Diterpenos/isolamento & purificação , Humanos , Raízes de Plantas , Relação Estrutura-Atividade
11.
Anal Chim Acta ; 1056: 79-87, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-30797464

RESUMO

Combination antiretroviral therapy (cART) regimens are recommended for HIV patients to better achieve and maintain plasma viral suppression. Despite adequate plasma viral suppression, HIV persists inside the brain, which is, in part thought to result from poor brain penetration of antiretroviral drugs. In this study, a simple and ultra-sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of tenofovir, emtricitabine, and dolutegravir in cell lysates of an immortalized human brain microvascular endothelial cell line (hCMEC/D3) was developed and validated. Analytes were separated on a reverse phase C18 column using water and 0.1% formic acid in acetonitrile as mobile phases. The analytes were detected using positive electrospray ionization mode with multiple reaction monitoring (MRM). The assay was linear in the concentration range of 0.1-100 ng mL-1 for all analytes. Intra- and inter-assay precision and accuracy were within ±13.33% and ±10.53%, respectively. This approach described herein was used to determine the intracellular accumulation of tenofovir, emtricitabine, dolutegravir simultaneously in hCMEC/D3 cells samples.


Assuntos
Fármacos Anti-HIV/análise , Encéfalo/citologia , Cromatografia Líquida/métodos , Células Endoteliais/citologia , Espaço Intracelular/química , Espectrometria de Massas em Tandem/métodos , Métodos Analíticos de Preparação de Amostras , Fármacos Anti-HIV/isolamento & purificação , Linhagem Celular , Emtricitabina/análise , Emtricitabina/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/análise , Compostos Heterocíclicos com 3 Anéis/isolamento & purificação , Humanos , Modelos Lineares , Oxazinas , Piperazinas , Piridonas , Reprodutibilidade dos Testes , Tenofovir/análise , Tenofovir/isolamento & purificação
12.
Bioorg Chem ; 83: 1-5, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30339860

RESUMO

Two new monoterpene indole alkaloids, naucleaoffines A (1) and B (2), together with six known alkaloids (3-8), were isolated from the stems and leaves of Nauclea officinalis. The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with the data reported in literature. All isolated compounds were evaluated for their anti-inflammatory activities and anti-HIV-1 activities. Compounds 1-8 exhibited significant inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro with IC50 values comparable to that of hydrocortisone. In addition, compounds 1-8 showed significant anti-HIV-1 activities with EC50 ranged from 0.06 to 2.08 µM. These findings suggest that the discoveries of these indole alkaloids with significant anti-inflammatory activities and anti-HIV-1 activities isolated from N. officinalis could be of great importance to the development of new anti-inflammatory and anti-HIV agents.


Assuntos
Fármacos Anti-HIV/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Alcaloides Indólicos/farmacologia , Monoterpenos/farmacologia , Rubiaceae/química , Animais , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Relação Dose-Resposta a Droga , HIV-1/efeitos dos fármacos , Alcaloides Indólicos/química , Alcaloides Indólicos/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Monoterpenos/química , Monoterpenos/isolamento & purificação , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Relação Estrutura-Atividade
13.
Fitoterapia ; 131: 265-271, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30414876

RESUMO

Six new xanthone-derived polyketides, named phomoxanthones F-K (1-6), along with three known ones, were isolated from Phomopsis sp. xy21, which was isolated as an endophytic fungus from the Thai mangrove Xylocarpus granatum. Phomoxanthone F (1) represents the first xanthone-derived polyketide containing a 10a-decarboxylated benzopyranone nucleus that was substituted by a 4-methyldihydrofuran-2(3H)-one moiety at C10a. Phomoxanthones G (2) and H (3) are highly oxidized xanthone-derived polyketides containing a novel 5-methyl-6-oxabicyclo[3.2.1]octane motif. This is the first report of a C6-O-C12 bridge in xanthone-derived polyketides. Additionally, a plausible biogenetic pathway for these xanthone-derived polyketides is proposed.


Assuntos
Ascomicetos/química , Meliaceae/microbiologia , Policetídeos/isolamento & purificação , Xantonas/isolamento & purificação , Fármacos Anti-HIV/isolamento & purificação , Linhagem Celular Tumoral , Endófitos/química , Humanos , Estrutura Molecular , Tailândia
14.
Bioorg Med Chem ; 26(23-24): 6050-6055, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30448257

RESUMO

Based on genome mining, a new lasso peptide specialicin was isolated from the extract of Streptomyces specialis. The structure of specialicin was established by ESI-MS and NMR analyses to be a lasso peptide with the length of 21 amino acids, containing an isopeptide bond and two disulfide bonds in the molecule. The stereochemistries of the constituent amino acids except for Trp were determined to be L and the stereochemistry of Trp at C-terminus was determined to be D. Three dimensional structure of specialicin was determined based on NOE experimental data, which indicated that specialicin possessed the similar conformational structure with siamycin I. Specialicin showed the antibacterial activity against Micrococcus luteus and the moderate anti-HIV activity against HIV-1 NL4-3. The biosynthetic gene cluster of specialicin was proposed from the genome sequence data of S. specialis.


Assuntos
Antibacterianos/farmacologia , Fármacos Anti-HIV/farmacologia , HIV/efeitos dos fármacos , Micrococcus luteus/efeitos dos fármacos , Peptídeos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Relação Dose-Resposta a Droga , Peptídeos e Proteínas de Sinalização Intercelular , Testes de Sensibilidade Microbiana , Conformação Molecular , Família Multigênica , Peptídeos/química , Peptídeos/genética , Peptídeos/isolamento & purificação , Streptomyces/química , Relação Estrutura-Atividade
15.
J Nat Prod ; 81(7): 1619-1627, 2018 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-30010341

RESUMO

A novel cycloartane triterpenoid alkaloid, kleinhospitine E (1), six new cycloartane triterpenoids (2-7), three known cycloartane triterpenoids (8-10), and taraxerone (11) were isolated from a methanol extract of Kleinhovia hospita. Their structures were elucidated by 1D- and 2D-NMR spectroscopy as well as HRMS analysis. The absolute configurations of all isolated compounds were determined from their ECD spectra by comparison with theoretical values. Kleinhospitine E (1) is the first cycloartane alkaloid possessing an unusual γ-lactam with an oxopropylidene side chain. Compounds 2, 3, and 6 were assigned as cycloartane triterpenoids with a 9α,10α-cyclopropyl ring, which is found rarely among naturally occurring compounds, while 4 and 5 were established as isomers of compound 3 containing a 21,23-diacetal side chain. Biological evaluation revealed that compounds 4 and 9 exhibited more potent antiproliferative activities against a multidrug-resistant tumor cell line compared with its parent chemosensitive cell line. Furthermore, compound 6 exhibited submicromolar anti-HIV activity.


Assuntos
Malvaceae/química , Extratos Vegetais/farmacologia , Triterpenos/isolamento & purificação , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Triterpenos/química , Triterpenos/farmacologia
16.
Viruses ; 10(7)2018 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-29954099

RESUMO

Natural products originating from marine and plant materials are a rich source of chemical diversity and unique antimicrobials. Using an established in vitro model of HIV-1 latency, we screened 257 pure compounds from a marine natural product library and identified 4 (psammaplin A, aplysiatoxin, debromoaplysiatoxin, and previously-described alotaketal C) that induced expression of latent HIV-1 provirus in both cell line and primary cell models. Notably, aplysiatoxin induced similar levels of HIV-1 expression as prostratin but at up to 900-fold lower concentrations and without substantial effects on cell viability. Psammaplin A enhanced HIV-1 expression synergistically when treated in combination with the protein kinase C (PKC) activator prostratin, but not the histone deacetylase inhibitor (HDACi) panobinostat, suggesting that psammaplin A functions as a latency-reversing agent (LRA) of the HDACi class. Conversely, aplysiatoxin and debromoaplysiatoxin synergized with panobinostat but not prostratin, suggesting that they function as PKC activators. Our study identifies new compounds from previously untested marine natural products and adds to the repertoire of LRAs that can inform therapeutic "shock-and-kill"-based strategies to eliminate latent HIV-infected reservoirs.


Assuntos
Fármacos Anti-HIV/farmacologia , Organismos Aquáticos/química , Produtos Biológicos/farmacologia , Descoberta de Drogas , HIV-1/efeitos dos fármacos , Latência Viral/efeitos dos fármacos , Fármacos Anti-HIV/isolamento & purificação , Produtos Biológicos/isolamento & purificação , Linfócitos T CD4-Positivos/virologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dissulfetos/farmacologia , Infecções por HIV/virologia , HIV-1/fisiologia , Ensaios de Triagem em Larga Escala , Humanos , Panobinostat/farmacologia , Ésteres de Forbol/farmacologia , Provírus , Tirosina/análogos & derivados , Tirosina/farmacologia , Ativação Viral/efeitos dos fármacos
17.
Plant Mol Biol ; 97(4-5): 357-370, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29948657

RESUMO

KEY MESSAGE: The potent anti-HIV microbicide griffithsin was expressed to high levels in tobacco chloroplasts, enabling efficient purification from both fresh and dried biomass, thus providing storable material for inexpensive production and scale-up on demand. The global HIV epidemic continues to grow, with 1.8 million new infections occurring per year. In the absence of a cure and an AIDS vaccine, there is a pressing need to prevent new infections in order to curb the disease. Topical microbicides that block viral entry into human cells can potentially prevent HIV infection. The antiviral lectin griffithsin has been identified as a highly potent inhibitor of HIV entry into human cells. Here we have explored the possibility to use transplastomic plants as an inexpensive production platform for griffithsin. We show that griffithsin accumulates in stably transformed tobacco chloroplasts to up to 5% of the total soluble protein of the plant. Griffithsin can be easily purified from leaf material and shows similarly high virus neutralization activity as griffithsin protein recombinantly expressed in bacteria. We also show that dried tobacco provides a storable source material for griffithsin purification, thus enabling quick scale-up of production on demand.


Assuntos
Fármacos Anti-HIV/metabolismo , Inibidores da Fusão de HIV/metabolismo , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Lectinas de Plantas/metabolismo , Tabaco/metabolismo , Fármacos Anti-HIV/isolamento & purificação , Cloroplastos/genética , Cloroplastos/metabolismo , Genoma de Cloroplastos/genética , Inibidores da Fusão de HIV/isolamento & purificação , Infecções por HIV/virologia , Humanos , Agricultura Molecular , Folhas de Planta/genética , Folhas de Planta/metabolismo , Lectinas de Plantas/genética , Lectinas de Plantas/isolamento & purificação , Tabaco/genética
18.
Bioorg Chem ; 79: 111-114, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29738969

RESUMO

A novel tetrahydrofuran derivative, trigonohowine (1), together with five known tetrahydrofuran derivatives (2-6), were isolated from the stems and leaves of Trigonostemon howii. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with the data reported in literature. Among them, trigonohowine (1) represents the first example of a new type of tetrahydrofuran derivative, possessing an unprecedented carbon skeleton containing 23 carbon atoms on the carbon skeleton and the known compouds (2-6) are rare tetrahydrofuran derivatives in the plant kingdom with various carbon skeletons. All isolated compounds were evaluated for their anti-HIV-1 activities. Compounds 1-6 showed significant anti-HIV-1 activities with EC50 ranged from 0.08 to 1.03 µM. These findings suggest that the discoveries of these tetrahydrofuran derivatives with significant anti-HIV-1 activities isolated from T. howii could be of great importance to the development of new anti-HIV agents.


Assuntos
Fármacos Anti-HIV/farmacologia , Euphorbiaceae/química , Furanos/farmacologia , HIV-1/efeitos dos fármacos , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Linhagem Celular , Furanos/química , Furanos/isolamento & purificação , Humanos , Estrutura Molecular , Folhas de Planta/química , Caules de Planta/química
19.
Chem Biodivers ; 15(5): e1700560, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29569369

RESUMO

Three new compounds (1 - 3), including two euphane type triterpenes, 24,24-dimethoxy-25,26,27-trinoreuphan-3ß-ol (1) and (24S)-24-hydroperoxyeupha-8,25-dien-3ß-ol (2), and an ent-atisine diterpene, ent-atisane-3α,16α,17-triol (3), were isolated from an acetone extract of the stems of Euphorbia antiquorum, together with eight known diterpenes (4 - 11). The structures of compounds (1 - 11) were elucidated using NMR and MS spectroscopic methods. Compound 7 showed moderate activity against HIV-1 replication in vitro (EC50 = 1.38 µm).


Assuntos
Fármacos Anti-HIV/farmacologia , Euphorbia/química , HIV-1/efeitos dos fármacos , Terpenos/farmacologia , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Linhagem Celular Transformada , Transformação Celular Viral/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Terpenos/química , Terpenos/isolamento & purificação , Replicação Viral/efeitos dos fármacos
20.
Chem Biodivers ; 15(5): e1700557, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29521032

RESUMO

Collagen is the most studied protein with a wide range of applications including pharmaceutical, biomedical, cosmetics, leather, and film industries due to its special characteristics that are high biocompatibility, good bioactivity, and weak antigenicity. Although collagen sources are abundant, the outbreak of varied diseases among land animals posed threat to its utilization in our daily life. Thus, a probe for an alternative source began, which in turn revealed the immense untapped marine sources, such as fish, jellyfish, and some marine Mammals. The present article deals with a brief description of collagen, its characteristics, marine sources, extraction, collagen peptides and their biological activities, potential use and application in various field.


Assuntos
Fármacos Anti-HIV/farmacologia , Anti-Hipertensivos/farmacologia , Antioxidantes/farmacologia , Pesquisa Biomédica , Colágeno/farmacologia , Animais , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Anti-Hipertensivos/química , Anti-Hipertensivos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Colágeno/química , Colágeno/isolamento & purificação , HIV-1/efeitos dos fármacos , Humanos , Envelhecimento da Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
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