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1.
Plant Cell ; 30(8): 1864-1886, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29967287

RESUMO

Plant specialized metabolism serves as a rich resource of biologically active molecules for drug discovery. The acylated flavonol glycoside montbretin A (MbA) and its precursor myricetin 3-O-(6'-O-caffeoyl)-glucosyl rhamnoside (mini-MbA) are potent inhibitors of human pancreatic α-amylase and are being developed as drug candidates to treat type-2 diabetes. MbA occurs in corms of the ornamental plant montbretia (Crocosmia x crocosmiiflora), but a system for large-scale MbA production is currently unavailable. Biosynthesis of MbA from the flavonol myricetin and MbA accumulation occur during early stages of corm development. We established myricetin 3-O-rhamnoside (MR), myricetin 3-O-glucosyl rhamnoside (MRG), and mini-MbA as the first three intermediates of MbA biosynthesis. Contrasting the transcriptomes of young and old corms revealed differentially expressed UDP-sugar-dependent glycosyltransferases (UGTs) and BAHD-acyltransferases (BAHD-ATs). UGT77B2 and UGT709G2 catalyze the consecutive glycosylation of myricetin to produce MR and of MR to give MRG, respectively. In addition, two BAHD-ATs, CcAT1 and CcAT2, catalyze the acylation of MRG to complete the formation of mini-MbA. Transcript profiles of UGT77B2, UGT709G2, CcAT1, and CcAT2 during corm development matched the metabolite profile of MbA accumulation. Expression of these enzymes in wild tobacco (Nicotiana benthamiana) resulted in the formation of a surrogate mini-MbA, validating the potential for metabolic engineering of mini-MbA in a heterologous plant system.


Assuntos
Aciltransferases/metabolismo , Flavonas/metabolismo , Glicosiltransferases/metabolismo , Tabaco/metabolismo , Trissacarídeos/metabolismo , Aciltransferases/genética , Glicosiltransferases/genética , Proteínas de Plantas/metabolismo
2.
J Med Chem ; 61(15): 6736-6747, 2018 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-29995409

RESUMO

Bifidenone is a novel natural tubulin polymerization inhibitor that exhibits antiproliferative activity against a range of human cancer cell lines, making it an attractive candidate for development. A synthetic route was previously developed to alleviate supply constraints arising from its isolation in microgram quantities from a Gabonese tree. Using that previously published route, we present here 42 analogues that were synthesized to examine the structure-activity relationship of bifidenone derivatives. In addition to in vitro cytotoxicity data, data from murine xenograft and pharmacokinetic studies were used to evaluate the analogues. Compounds 45b and 46b were found to demonstrate promising efficacy in murine xenograft experiments, and 46b had significantly more potent in vitro antiproliferative activity against taxane-resistant cell lines compared to that of paclitaxel.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Lignanas/química , Lignanas/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Camundongos , Multimerização Proteica/efeitos dos fármacos , Estrutura Quaternária de Proteína , Relação Estrutura-Atividade , Tubulina (Proteína)/química , Ensaios Antitumorais Modelo de Xenoenxerto
3.
J Nat Prod ; 80(3): 616-624, 2017 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-28335606

RESUMO

The pursuit of structurally novel compounds has led to the isolation of a series of neolignans (2-6), for which the structures have been determined from microgram quantities using microcryoprobe NMR technology. Compounds 2-6 provided some unexpectedly clear structure-activity relationship data, with compound 2 demonstrating significantly more potency in the in vitro cytotoxicity assay than the other analogues. Further screening found that compound 2 induces apoptosis with activation of caspase 3/7. The NCI Compare algorithm suggested that compound 2 acts through the inhibition of tubulin/microtubule dynamics. Compound 2 was confirmed to be a tubulin polymerization inhibitor that binds directly to tubulin.


Assuntos
Antineoplásicos/farmacologia , Lignanas/farmacologia , Moduladores de Tubulina/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lignanas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Relação Estrutura-Atividade , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/química
4.
J Org Chem ; 82(8): 4235-4241, 2017 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-28351141

RESUMO

The first total synthesis of bifidenone, a novel natural tubulin polymerization inhibitor, has been achieved in 12 steps starting from commercially available 1,4-dioxaspiro[4.5]decan-8-one. The synthesis includes a newly developed method to generate the dihydrobenzodioxolone core by palladium-catalyzed aerobic dehydrogenation. The three stereocenters were installed with an AD-mix-ß dihydroxylation step followed by a late-stage palladium-catalyzed decarboxylation-allylation procedure. The absolute stereochemistry of 3 was determined via 13a by single-crystal X-ray analysis.

5.
ACS Chem Biol ; 11(5): 1445-51, 2016 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-26930136

RESUMO

Natural product metabolic engineering potentially offers sustainable and affordable access to numerous valuable molecules. However, challenges in characterizing and assembling complex biosynthetic pathways have prevented more rapid progress in this field. The anticancer agent Taxol represents an excellent case study. Assembly of a biosynthetic pathway for Taxol has long been stalled at its first functionalization, putatively an oxygenation performed by the cytochrome P450 CYP725A4, due to confounding characterizations. Here, through combined in vivo (Escherichia coli), in vitro (lipid nanodisc), and metabolite stability assays, we verify the presence and likely cause of this enzyme's inherent promiscuity. Thereby, we remove the possibility that promiscuity simply existed as an artifact of previous metabolic engineering approaches. Further, spontaneous rearrangement and the stabilizing effect of a hydrophobic overlay suggest a potential role for nonenzymatic chemistry in Taxol's biosynthesis. Taken together, this work confirms taxadiene-5α-ol as a primary enzymatic product of CYP725A4 and provides direction for future Taxol metabolic and protein engineering efforts.


Assuntos
Alcenos/metabolismo , Antineoplásicos Fitogênicos/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Diterpenos/metabolismo , Escherichia coli/enzimologia , Paclitaxel/metabolismo , Taxus/enzimologia , Alcenos/química , Antineoplásicos Fitogênicos/química , Vias Biossintéticas , Diterpenos/química , Escherichia coli/química , Escherichia coli/metabolismo , Fermentação , Engenharia Metabólica , Modelos Moleculares , Oxirredução , Paclitaxel/química , Especificidade por Substrato , Taxus/química , Taxus/metabolismo
6.
Org Biomol Chem ; 13(39): 9957-62, 2015 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-26381222

RESUMO

A strategy for the dereplication of a complete or a partial structure using (1)H NMR, (1)H-(13)C HSQC and (1)H-(1)H COSY spectral data, a molecular formula composition range and structural fragments against a massive database of about 22 million compounds is considered. As the increasing availability of public online databases containing natural products continues to grow the potential of utilizing these resources for dereplication purposes increases. This work examines approaches for NMR dereplication of natural products and includes a comparison with approaches for molecular formula and mass-based dereplication. The strategy is an application of computer-assisted structure elucidation using ACD/Structure Elucidator and data obtained from the ChemSpider database hosted by the Royal Society of Chemistry.


Assuntos
Produtos Biológicos/química , Espectroscopia de Ressonância Magnética/métodos , Bases de Dados de Compostos Químicos , Bases de Dados de Produtos Farmacêuticos , Estrutura Molecular
7.
J Nat Prod ; 78(8): 2074-86, 2015 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-26287548

RESUMO

The compass plant, Silphium laciniatum, is an iconic perennial plant of the North American tallgrass prairie. The plants of the tallgrass prairie historically have been subjected to a number of biological and environmental stresses. Among the adaptations developed by S. laciniatum is a large deep taproot. An investigation of the secondary metabolites found in the root of a S. laciniatum specimen has led to the identification of 15 new terpenoids (3-8, 10-17, and 22), which were screened for cytotoxic activity in the NCI-H460 human large-cell lung carcinoma cell line.


Assuntos
Asteraceae/química , Terpenos/isolamento & purificação , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Missouri , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Terpenos/química , Terpenos/farmacologia
8.
J Am Chem Soc ; 137(33): 10603-9, 2015 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-26230368

RESUMO

The structural scaffolds of many complex natural products are produced by multifunctional type I polyketide synthase (PKS) enzymes that operate as biosynthetic assembly lines. The modular nature of these mega-enzymes presents an opportunity to construct custom biocatalysts built in a lego-like fashion by inserting, deleting, or exchanging native or foreign domains to produce targeted variants of natural polyketides. However, previously engineered PKS enzymes are often impaired resulting in limited production compared to native systems. Here, we show a versatile method for generating and identifying functional chimeric PKS enzymes for synthesizing custom macrolactones and macrolides. PKS genes from the pikromycin and erythromycin pathways were hybridized in Saccharomyces cerevisiae to generate hybrid libraries. We used a 96-well plate format for plasmid purification, transformations, sequencing, protein expression, in vitro reactions and analysis of metabolite formation. Active chimeric enzymes were identified with new functionality. Streptomyces venezuelae strains that expressed these PKS chimeras were capable of producing engineered macrolactones. Furthermore, a macrolactone generated from selected PKS chimeras was fully functionalized into a novel macrolide analogue. This method permits the engineering of PKS pathways as modular building blocks for the production of new antibiotic-like molecules.


Assuntos
Evolução Molecular , Recombinação Homóloga , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Eritromicina/metabolismo , Escherichia coli/genética , Macrolídeos/metabolismo , Engenharia de Proteínas , Saccharomyces cerevisiae/genética , Streptomyces/metabolismo
9.
Plant J ; 83(5): 783-93, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26119826

RESUMO

Grindelia robusta or gumweed, is a medicinal herb of the sunflower family that forms a diverse suite of diterpenoid natural products. Its major constituents, grindelic acid and related grindelane diterpenoids accumulate in a resinous exudate covering the plants' surfaces, most prominently the unopened composite flower. Recent studies demonstrated potential pharmaceutical applications for grindelic acid and its synthetic derivatives. Mining of the previously published transcriptome of G. robusta flower tissue identified two additional diterpene synthases (diTPSs). We report the in vitro and in vivo functional characterization of an ent-kaurene synthase of general metabolism (GrTPS4) and a class II diTPS (GrTPS2) of specialized metabolism that converts geranylgeranyl diphosphate (GGPP) into labda-7,13E-dienyl diphosphate as verified by nuclear magnetic resonance (NMR) analysis. Tissue-specific transcript abundance of GrTPS2 in leaves and flowers accompanied by the presence of an endocyclic 7,13 double bond in labda-7,13E-dienyl diphosphate suggest that GrTPS2 catalyzes the first committed reaction in the biosynthesis of grindelic acid and related grindelane metabolites. With the formation of labda-7,13E-dienyl diphosphate, GrTPS2 adds an additional function to the portfolio of monofunctional class II diTPSs, which catalytically most closely resembles the bifunctional labda-7,13E-dien-15-ol synthase of the lycopod Selaginella moellendorffii. Together with a recently identified functional diTPS pair of G. robusta producing manoyl oxide, GrTPS2 lays the biosynthetic foundation of the diverse array of labdane-related diterpenoids in the genus Grindelia. Knowledge of these natural diterpenoid metabolic pathways paves the way for developing biotechnology approaches toward producing grindelic acid and related bioproducts.


Assuntos
Alquil e Aril Transferases/metabolismo , Diterpenos de Caurano/metabolismo , Diterpenos/metabolismo , Grindelia/genética , Grindelia/metabolismo , Liases Intramoleculares/metabolismo , Proteínas de Plantas/metabolismo , Alquil e Aril Transferases/genética , Diterpenos de Caurano/genética , Perfilação da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Liases Intramoleculares/genética , Dados de Sequência Molecular , Filogenia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Tabaco/genética
10.
Plant J ; 82(6): 991-1003, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25939370

RESUMO

Steroid alkaloids have been shown to elicit a wide range of pharmacological effects that include anticancer and antifungal activities. Understanding the biosynthesis of these molecules is essential to bioengineering for sustainable production. Herein, we investigate the biosynthetic pathway to cyclopamine, a steroid alkaloid that shows promising antineoplastic activities. Supply of cyclopamine is limited, as the current source is solely derived from wild collection of the plant Veratrum californicum. To elucidate the early stages of the pathway to cyclopamine, we interrogated a V. californicum RNA-seq dataset using the cyclopamine accumulation profile as a predefined model for gene expression with the pattern-matching algorithm Haystack. Refactoring candidate genes in Sf9 insect cells led to discovery of four enzymes that catalyze the first six steps in steroid alkaloid biosynthesis to produce verazine, a predicted precursor to cyclopamine. Three of the enzymes are cytochromes P450 while the fourth is a γ-aminobutyrate transaminase; together they produce verazine from cholesterol.


Assuntos
Enzimas/metabolismo , Alcaloides de Veratrum/metabolismo , Veratrum/genética , Veratrum/metabolismo , 4-Aminobutirato Transaminase/genética , 4-Aminobutirato Transaminase/metabolismo , Algoritmos , Animais , Vias Biossintéticas , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Enzimas/genética , Perfilação da Expressão Gênica/métodos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Análise de Sequência de RNA/métodos , Células Sf9 , Transcriptoma
11.
Nat Prod Commun ; 9(8): 1129-30, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25233589

RESUMO

One new and seven known diterpenes were identified from an antibacterial chromatographic fraction of Taxodium ascendens. Of these, demethylcryptojaponol (2), 6-hydroxysalvinolone (3), hydroxyferruginol (4), and hinokiol (5) demonstrated potent activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). These compounds represent a class of synthetically accessible compounds that could be further developed for treatment of drug-resistant bacterial infections.


Assuntos
Antibacterianos/farmacologia , Diterpenos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Extratos Vegetais/farmacologia , Taxodium/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
12.
PLoS One ; 9(7): e103223, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25061748

RESUMO

Galanthamine is an Amaryllidaceae alkaloid used to treat the symptoms of Alzheimer's disease. This compound is primarily isolated from daffodil (Narcissus spp.), snowdrop (Galanthus spp.), and summer snowflake (Leucojum aestivum). Despite its importance as a medicine, no genes involved in the biosynthetic pathway of galanthamine have been identified. This absence of genetic information on biosynthetic pathways is a limiting factor in the development of synthetic biology platforms for many important botanical medicines. The paucity of information is largely due to the limitations of traditional methods for finding biochemical pathway enzymes and genes in non-model organisms. A new bioinformatic approach using several recent technological improvements was applied to search for genes in the proposed galanthamine biosynthetic pathway, first targeting methyltransferases due to strong signature amino acid sequences in the proteins. Using Illumina sequencing, a de novo transcriptome assembly was constructed for daffodil. BLAST was used to identify sequences that contain signatures for plant O-methyltransferases in this transcriptome. The program HAYSTACK was then used to identify methyltransferases that fit a model for galanthamine biosynthesis in leaf, bulb and inflorescence tissues. One candidate gene for the methylation of norbelladine to 4'-O-methylnorbelladine in the proposed galanthamine biosynthetic pathway was identified. This methyltransferase cDNA was expressed in E. coli and the protein purified by affinity chromatography. The resulting protein was found to be a norbelladine 4'-O-methyltransferase (NpN4OMT) of the proposed galanthamine biosynthetic pathway.


Assuntos
Alcaloides/metabolismo , Galantamina/metabolismo , Narcissus/enzimologia , Proteína O-Metiltransferase/genética , Alcaloides/genética , Alcaloides/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Sequência de Aminoácidos , Clonagem Molecular , DNA Complementar , Escherichia coli , Galantamina/genética , Galantamina/uso terapêutico , Humanos , Narcissus/química , Narcissus/genética , Proteína O-Metiltransferase/isolamento & purificação , Proteína O-Metiltransferase/metabolismo
13.
PLoS One ; 9(7): e100474, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25004127

RESUMO

There is continuing international interest in exploring and developing the therapeutic potential of marine-derived small molecules. Balancing the strategies for ocean based sampling of source organisms versus the potential to endanger fragile ecosystems poses a substantial challenge. In order to mitigate such environmental impacts, we have developed a deployable artificial sponge. This report provides details on its design followed by evidence that it faithfully recapitulates traditional natural product collection protocols. Retrieving this artificial sponge from a tropical ecosystem after deployment for 320 hours afforded three actin-targeting jasplakinolide depsipeptides that had been discovered two decades earlier using traditional sponge specimen collection and isolation procedures. The successful outcome achieved here could reinvigorate marine natural products research, by producing new environmentally innocuous sources of natural products and providing a means to probe the true biosynthetic origins of complex marine-derived scaffolds.


Assuntos
Produtos Biológicos , Biomimética/métodos , Descoberta de Drogas , Poríferos/química , Animais , Produtos Biológicos/química , Biomimética/instrumentação , Depsipeptídeos/química , Ecossistema
14.
Plant J ; 79(6): 914-27, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24990389

RESUMO

Marrubium vulgare (Lamiaceae) is a medicinal plant whose major bioactive compounds, marrubiin and other labdane-related furanoid diterpenoids, have potential applications as anti-diabetics, analgesics or vasorelaxants. Metabolite and transcriptome profiling of M. vulgare leaves identified five different candidate diterpene synthases (diTPSs) of the TPS-c and TPS-e/f clades. We describe the in vitro and in vivo functional characterization of the M. vulgare diTPS family. In addition to MvEKS ent-kaurene synthase of general metabolism, we identified three diTPSs of specialized metabolism: MvCPS3 (+)-copalyl diphosphate synthase, and the functional diTPS pair MvCPS1 and MvELS. In a sequential reaction, MvCPS1 and MvELS produce a unique oxygenated diterpene scaffold 9,13-epoxy-labd-14-ene en route to marrubiin and an array of related compounds. In contrast with previously known diTPSs that introduce a hydroxyl group at carbon C-8 of the labdane backbone, the MvCPS1-catalyzed reaction proceeds via oxygenation of an intermediate carbocation at C-9, yielding the bicyclic peregrinol diphosphate. MvELS belongs to a subgroup of the diTPS TPS-e/f clade with unusual ßα-domain architecture. MvELS is active in vitro and in vivo with three different prenyl diphosphate substrates forming the marrubiin precursor 9,13-epoxy-labd-14-ene, as identified by nuclear magnetic resonance (NMR) analysis, manoyl oxide and miltiradiene. MvELS fills a central position in the biosynthetic system that forms the foundation for the diverse repertoire of Marrubium diterpenoids. Co-expression of MvCPS1 and MvELS in engineered E. coli and Nicotiana benthamiana offers opportunities for producing precursors for an array of biologically active diterpenoids.


Assuntos
Diterpenos/metabolismo , Marrubium/enzimologia , Alquil e Aril Transferases , Sequência de Aminoácidos , Escherichia coli/genética , Marrubium/química , Marrubium/genética , Dados de Sequência Molecular , Organofosfatos , Filogenia , Proteínas de Plantas , Plantas Medicinais
15.
J Nat Prod ; 77(6): 1438-44, 2014 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-24922615

RESUMO

Species extinction is tantamount to loss of chemical diversity, and so it is important to seize all opportunities to study species on the brink of extinction. Such studies are often hampered by the limited material available, but that obstacle is surmountable through collaboration with botanical gardens and advances in instrumentation. The goldenrod Solidago shortii is one example of an endangered species native to the United States. From S. shortii, one known diterpene (1), two new diterpenes (2 and 3), and three new hydrolysis products (4-6) are described. This work was made possible through collaboration with the Missouri Botanical Garden and with the use of highly sensitive microcryoprobe NMR technology for structure elucidation and VCD spectroscopy for the determination of absolute configuration.


Assuntos
Diterpenos/isolamento & purificação , Solidago/química , Cristalografia por Raios X , Diterpenos/química , Espécies em Perigo de Extinção , Missouri , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
16.
Phytochemistry ; 98: 216-22, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24361290
17.
J Nat Prod ; 76(9): 1592-7, 2013 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-23978065

RESUMO

The first study of the chemical constituents of Combretum inflatum has resulted in the isolation of seven new acetylated dammarane-type bisdesmosides (1-7). Their structures were determined from microgram quantities on hand using Bruker BioSpin TCI 1.7 mm MicroCryoProbe technology, ESIMS, and comparison to data found in the literature. Compounds 1-7 were screened for inhibition of an Escherichia coli strain UTI89 biofilm, MRSA inhibition, and cytotoxicity in NCI-H460 human lung cancer cells. Compounds 3-7 reduced the growth of MRSA at 16 µg/mL by 71-45%, and compound 7 had an IC50 value of 3.9 µM in NCI-H460.


Assuntos
Antibacterianos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Combretaceae/química , Triterpenos/isolamento & purificação , Acetilação , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Escherichia coli/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Missouri , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Triterpenos/química , Triterpenos/farmacologia
18.
Phytochemistry ; 82: 172-5, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22805176

RESUMO

Seven stilbenes and one alkylresorcinol were isolated from the orchid Phragmipedium calurum during a screen for anticancer compounds. They were evaluated for antiproliferative activity against multiple human cancer cell lines, and two displayed moderate activity against several cell lines.


Assuntos
Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Orchidaceae/química , Resorcinóis/isolamento & purificação , Resorcinóis/farmacologia , Estilbenos/isolamento & purificação , Estilbenos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Resorcinóis/química , Estilbenos/química
19.
J Nat Prod ; 75(7): 1319-25, 2012 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-22758788

RESUMO

High-throughput natural products chemistry methods have facilitated the isolation of eight new (1-8) and two known (9 and 10) beilschmiedic acid derivatives from the leaves of a Gabonese species of Beilschmiedia. Compounds 3-10 were isolated in microgram quantities, and the NMR data for structure elucidation and dereplication were acquired utilizing a Bruker BioSpin TCI 1.7 mm MicroCryoProbe. All of the compounds were screened for cytotoxic and antibacterial activity against NCI-H460 human lung cancer cells and a clinical isolate of methicillin-resistant Staphylococcus aureus, respectively. This is the first report of cytotoxic activity for the endiandric/beilschmiedic acid class of compounds.


Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Ácidos Carboxílicos/isolamento & purificação , Ácidos Carboxílicos/farmacologia , Ácidos Graxos/isolamento & purificação , Ácidos Graxos/farmacologia , Lauraceae/química , Antibacterianos/química , Antineoplásicos/química , Ácidos Carboxílicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Ácidos Graxos/química , Gabão , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Staphylococcus aureus/efeitos dos fármacos
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