RESUMO
Alzheimer's disease (AD) and diabetes are non-communicable diseases with global impacts. Inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are suitable therapies for AD, while α-amylase and α-glucosidase inhibitors are employed as antidiabetic agents. Compounds were isolated from the medicinal plant Terminalia macroptera and evaluated for their AChE, BChE, α-amylase, and α-glucosidase inhibitions. From 1H and 13C NMR data, the compounds were identified as 3,3'-di-O-methyl ellagic acid (1), 3,3',4'-tri-O-methyl ellagic acid-4-O-ß-D-xylopyranoside (2), 3,3',4'-tri-O-methyl ellagic acid-4-O-ß-D-glucopyranoside (3), 3,3'-di-O-methyl ellagic acid-4-O-ß-D-glucopyranoside (4), myricetin-3-O-rhamnoside (5), shikimic acid (6), arjungenin (7), terminolic acid (8), 24-deoxysericoside (9), arjunglucoside I (10), and chebuloside II (11). The derivatives of ellagic acid (1-4) showed moderate to good inhibition of cholinesterases, with the most potent being 3,3'-di-O-methyl ellagic acid, with IC50 values of 46.77 ± 0.90 µg/mL and 50.48 ± 1.10 µg/mL against AChE and BChE, respectively. The compounds exhibited potential inhibition of α-amylase and α-glucosidase, especially the phenolic compounds (1-5). Myricetin-3-O-rhamnoside had the highest α-amylase inhibition with an IC50 value of 65.17 ± 0.43 µg/mL compared to acarbose with an IC50 value of 32.25 ± 0.36 µg/mL. Two compounds, 3,3'-di-O-methyl ellagic acid (IC50 = 74.18 ± 0.29 µg/mL) and myricetin-3-O-rhamnoside (IC50 = 69.02 ± 0.65 µg/mL), were more active than the standard acarbose (IC50 = 87.70 ± 0.68 µg/mL) in the α-glucosidase assay. For α-glucosidase and α-amylase, the molecular docking results for 1-11 reveal that these compounds may fit well into the binding sites of the target enzymes, establishing stable complexes with negative binding energies in the range of -4.03 to -10.20 kcalmol-1. Though not all the compounds showed binding affinities with cholinesterases, some had negative binding energies, indicating that the inhibition was thermodynamically favorable.
Assuntos
Acetilcolinesterase , Inibidores da Colinesterase , Hipoglicemiantes , Simulação de Acoplamento Molecular , Extratos Vegetais , Terminalia , alfa-Amilases , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , Acetilcolinesterase/metabolismo , Acetilcolinesterase/química , Terminalia/química , Humanos , Butirilcolinesterase/metabolismo , alfa-Glucosidases/metabolismo , alfa-Glucosidases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Estrutura MolecularRESUMO
A new vobasine-tryptamine-based monoterpene indole alkaloid pseudodimer was isolated from the stem bark of Voacanga africana. As a minor constituent occurring in a thoroughly investigated plant, this molecule was targeted based on a molecular networking strategy and a rational MS2-guided phytochemical investigation led to its isolation. Its structure was formally established based on HRMS, 1D/2D NMR data, and the application of the tool Small Molecule Accurate Recognition Technology (SMART 2.0). Its absolute configuration was assigned by the exciton chirality method and TD-DFT ECD calculations. Besides featuring an unprecedented intermonomeric linkage in the small group of vobasine/tryptamine hybrids, pyrrovobasine also represents the first pyrraline-containing representative in the whole monoterpene indole alkaloids group. Biosynthetic hypotheses possibly underpinning these structural oddities are proposed here.
Assuntos
Alcaloides Indólicos/química , Aprendizado de Máquina , Monoterpenos/química , Norleucina/análogos & derivados , Pirróis/química , Alquilação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Norleucina/química , Voacanga/químicaRESUMO
Voatriafricanines A and B (1 and 2), the first examples of vobasine-aspidosperma-aspidosperma monoterpene trisindole alkaloids, were isolated from the stem barks of Voacanga africana, guided by a molecular networking strategy. Their structures, including absolute configurations, were elucidated by spectroscopic methods and ECD calculations. Compounds 1 and 2 possess intramolecular hydrogen bonding, sufficiently robust to transfer homonuclear and heteronuclear magnetizations. Compound 1 exhibited potent antimycobacterial activity with no discernible cytotoxic activity.
Assuntos
Antibacterianos/farmacologia , Alcaloides Indólicos/farmacologia , Voacanga/química , Antibacterianos/isolamento & purificação , Camarões , Alcaloides Indólicos/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Casca de Planta/químicaRESUMO
A new prenylated xanthone, 1,3,5,8-tetrahydroxy-2-(3-methybut-2-enyl)-4-(3,7-dimethylocta-2,6-dienyl) xanthone (1), and a new benzophenone (2), together with four known xanthone derivatives, cheffouxanthone (3), smeathxanthone A (4), smeathxanthone B (5), ananixanthone (6), and two pentacyclic triterpenes, epi-friedelinol (7) and friedelin (8), were isolated from the stem bark of Garcinia smeathmannii. The structures of the compounds were elucidated on the basis of 1D and 2D NMR experiments, and compound 2 was further characterized and confirmed by single X-ray analysis. Compounds 1, 2, and 3 exhibited the most prominent antibacterial activity against gram-positive Enterococcus faecalis with minimal inhibitory concentration values of 8, 8, and 2 µg/mL, respectively, while compounds 1, 3, 4, and 6 showed the capacity to scavenge free radicals.
Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Benzofenonas/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Garcinia/química , Monoterpenos/farmacologia , Extratos Vegetais/farmacologia , Xantonas/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Benzofenonas/química , Benzofenonas/isolamento & purificação , Enterococcus faecalis/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Estrutura Molecular , Monoterpenos/química , Monoterpenos/isolamento & purificação , Casca de Planta , Extratos Vegetais/química , Caules de Planta , Triterpenos/química , Triterpenos/isolamento & purificação , Xantonas/química , Xantonas/isolamento & purificaçãoRESUMO
A new compound, named banganxanthone C (=12-(1,1-dimethylprop-2-en-1-yl)-5,10-dihydroxy-9-methoxy-2-methyl-2-(4-methylpent-3-en-1-yl)-2H,6H-pyrano[3,2-b]xanthen-6-one; 4), together with five known compounds, were isolated from the leaves of Garcinia polyantha. The structures of the compounds were elucidated on the basis of 1D- and 2D-NMR spectroscopy. Among the known compounds, two were xanthones, one was a pentacyclic triterpene, one sterol, and one benzophenone derivative. Isoxanthochymol (2) and 4-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-1,5,8-trihydroxy-3-methoxy-9H-xanthen-9-one (3) exhibited significant antiproliferative activity against the leukemia cell line TPH-1 with IC50 inhibition values of 1.5 and 2.8â µg/ml, respectively. The cytotoxic activity was found to be related to apoptosis induction.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Clusiaceae/química , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Folhas de Planta/química , Xantonas/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Compostos Heterocíclicos de 4 ou mais Anéis/química , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Compostos Heterocíclicos de 4 ou mais Anéis/toxicidade , Humanos , Concentração Inibidora 50 , Células MCF-7 , Estrutura Molecular , Relação Estrutura-Atividade , Xantonas/química , Xantonas/isolamento & purificação , Xantonas/toxicidadeRESUMO
A new α-pyrone, asperpyrone (1) and two known compounds, stigmasterol (2) and 7-hydroxy-3-(2,3-dihydroxybutyl)-1(3H)-Isobenzofuranone (3) were isolated from the solid rice culture of the endophytic fungus Aspergillus sp., an endophytic fungus isolated from the fresh inner tissue of the barks of Garicinia smeathmannii. Their structures were determined by extensive spectral analysis including 1 D and 2 D NMR, HRESIMS and single-crystal X-ray crystallographic analysis. Asperpyrone (1) was tested against an axenic culture of Entamoeba moshkovskii, but did not exhibit any significant amoebicidal activity.
Assuntos
Aspergillus , Pironas , Estrutura Molecular , Aspergillus/química , Espectroscopia de Ressonância Magnética , Cristalografia por Raios XRESUMO
Investigation of the leaves of Bauhinia thonningii Schum led to the isolation and identification of a new flavonol derivative, 6-C-methylquercetin-3,4'-dimethyl ether (1) together with eleven known compounds (2-13), with two of them (10 and 11) obtained as a mixture. Their structures were established by extensive spectroscopic analyses. Antibacterial activity of compound 1 as well as the reference antibiotic, ciprofloxacin was tested on Gram-negative multidrug-resistant bacteria overexpressing active efflux pumps, and against methicillin-resistant strains of Staphylococcus aureus (MRSA). Samples were tested alone and in combination with an efflux pump inhibitor (EPI), phenylalanine-arginine-ß-naphthylamide (PAßN). Results show that when compound 1 was tested alone, its inhibitory effects were obtained on 7/10 tested bacteria with the highest MIC value of 128 µg/mL whilst in the presence of EPI, this activity significantly increase in all the 10 bacteria. An interesting antibacterial activity was obtained with compound 1 against Klebsiella pneumoniae ATCC11296 (MIC of 4 µg/mL), KP55 and Staphylococcus aureus MRSA6 in the presence of the PaßN.
RESUMO
A new flavanone-chromone biflavonoid, preussianone (1), has been isolated from the leaves of Garcinia preussii, along with four known biflavonoids. The absolute stereostructures were elucidated by chemical, spectroscopic, and chiroptical methods. The biological properties of the new biflavonoid against several bacterial strains were evaluated.
Assuntos
Biflavonoides/química , Flavanonas/química , Garcinia/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Biflavonoides/isolamento & purificação , Biflavonoides/farmacologia , Flavanonas/isolamento & purificação , Flavanonas/farmacologiaRESUMO
A new xanthone, mboudiexanthone (1), together with five known compounds, euxanthone (2), isogarcinol (3), garcinol (4), betulinic acid (5) and zeorin (6) were isolated from the leaves of Garcinia nobilis Engl. The structures were determined by 1D and 2D NMR techniques and X-ray diffraction for 6. The in vitro antiproliferative properties of isolated compounds were evaluated against the human breast cancer cell line MCF-7. All compounds showed an antiproliferative activity with an IC50 value down to â¼11 µM for isogarcinol.
Assuntos
Garcinia , Xantonas , Humanos , Estrutura Molecular , Extratos Vegetais/farmacologia , Folhas de Planta , Xantonas/farmacologiaRESUMO
The new compounds guttiferone O ( 1) and 3-methoxycheffouxanthone ( 2) have been isolated from the seeds of Garcinia afzelii Engl., together with nine known compounds: 2-hydroxy-1,7-dimethoxyxanthone ( 3), smeathxanthone A ( 4), 1,5-dihydroxyxanthone ( 5), 1,6-dihydroxy-5-methoxyxanthone ( 6), cheffouxanthone ( 7), 1,3,5-trihydroxyxanthone ( 8), smeathxanthone B ( 9), isoxanthochymol ( 10) and guttiferone E ( 11). Their structures were elucidated by means of 1D and 2D-NMR techniques. All the isolates showed high cytotoxic activity and were found inactive when tested against HIV and influenza viruses.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Benzofenonas/isolamento & purificação , Garcinia/química , Xantonas/isolamento & purificação , Antivirais/isolamento & purificação , Avaliação Pré-Clínica de Medicamentos , Sementes/químicaRESUMO
The methanol extract from the stem bark of Diospyros sanza-minika as well as five norbergenin derivatives isolated from this crude extract were evaluated for their in vitro activity against Plasmodium falciparum K1 and cytotoxicity on MRC-5 cells. 4-O-(3'-methylgalloyl)norbergenin was found to be the most potent compound (IC(50) 0.6 µg/mL; CC(50) 24.7 µg/mL), followed by 4-O-galloylnorbergenin (IC(50) 3.9 µg/mL; CC(50) > 64 µg/mL) and 11-O-p-hydroxy-benzoyl-norbergenin (IC(50) 4.9 µg/mL; CC(50) > 64 µg/mL). Norbergenin and 4-O-syringoylnorbergenin were inactive (IC(50) > 32 µg/mL; CC(50) > 64 µg/mL). The antimalarial activity of the pure constituents and of the methanol extract from the stem bark of Diospyros sanza-minika is reported for the first time. The results provide interesting baseline information for the potential use of the crude extract well as some of the isolated compounds in the search for novel antimalarial compounds.
Assuntos
Antimaláricos/farmacologia , Benzopiranos/farmacologia , Diospyros/química , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/isolamento & purificação , Benzopiranos/isolamento & purificação , Linhagem Celular , Humanos , Estrutura Molecular , Casca de Planta/química , Extratos Vegetais/farmacologiaRESUMO
Three xanthones, polyanxanthone A (1), B (2) and C (3) have been isolated from the methanol extract of the wood trunk of Garcinia polyantha, along with five known xanthones: 1,3,5-trihydroxyxanthone (4); 1,5-dihydroxyxanthone (5); 1,3,6,7-tetrahydroxyxanthone (6); 1,6-dihydroxy-5-methoxyxanthone (7) and 1,3,5,6-tetrahydroxyxanthone (8). Their structures were determined by means of 1D- and 2D-NMR techniques. Some of the above compounds were screened for their anticholinesterase activity on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes.
Assuntos
Garcinia/química , Extratos Vegetais/química , Xantonas/química , Acetilcolinesterase/metabolismo , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Espectroscopia de Ressonância Magnética , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Madeira/química , Xantonas/isolamento & purificação , Xantonas/farmacologiaRESUMO
Eight compounds were isolated from the roots of Garcinia polyantha, and identified. Two of them, the xanthone garciniaxanthone I (1), and the triterpene, named garcinane (2), are reported as new natural products. The structures of the new compounds were elucidated on the basis of 1D and 2D NMR spectroscopic studies. The structure of compound 1 was confirmed by X-ray crystallography. Among the remaining six known compounds, three were known xanthones [smeathxanthone A (3), smeathxanthone B (4), and chefouxanthone (5)], one benzophenone [isoxanthochymol (6)], one triterpene [magnificol], and one sterol [beta-sitosterol]. The in vitro antimalarial activity of isoxanthochymol (6) against Plasmodium falciparum shows strong chemosuppression of parasitic growth.
Assuntos
Antimaláricos/isolamento & purificação , Garcinia/química , Plasmodium falciparum/efeitos dos fármacos , Triterpenos/isolamento & purificação , Xantonas/isolamento & purificação , Animais , Antimaláricos/química , Antimaláricos/farmacologia , Cristalografia por Raios X , Malária Falciparum/parasitologia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Rotação Ocular , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Plasmodium falciparum/isolamento & purificação , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Triterpenos/química , Triterpenos/farmacologia , Xantonas/química , Xantonas/farmacologiaRESUMO
One new depsidone, polyanthadepsidone A (1), together with four known compounds were isolated from the dichloromethane extract of the leaves of Garcinia polyantha. The structures of all compounds were determined by comprehensive analyses of their 1D and 2D NMR and EI mass spectral data. All the isolates exhibited suppressive effect on phagocytosis response upon activation with serum opsonised zymosan in the IC50 range of 4.5-23.80 µM, tested in vitro for oxidative burst studies of whole blood.
Assuntos
Depsídeos/química , Garcinia/química , Lactonas/química , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Fagocitose/efeitos dos fármacos , Extratos Vegetais/química , Folhas de Planta/química , Explosão Respiratória/efeitos dos fármacos , Zimosan/farmacologiaRESUMO
Phytochemical investigation of the twigs of Garcinia nobilis led to the isolation of a new xanthone, named l-hydroxy-2,5-dimethoxyxanthone (1), together with 15 known compounds (2-16). The structures of the new and known compounds were established by means of spectroscopic methods and by comparison with previously reported data. The structure of compound 1 was confirmed by X-ray diffraction data. Compounds 1-16 were tested for their cytotoxic activity against human cervix carcinoma cell line KB-3-1. Compounds 5 and 11 showed moderate activity while others showed weak biological activity in these cytotoxicity assays. Compounds 4 and 9 were found to be inactive.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Garcinia/química , Xantonas/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Camarões , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Xantonas/química , Xantonas/farmacologiaRESUMO
The microbial transformation of a steroidal alkaloid, dictyophlebine (1) with Rhizopus stolonifer (ATCC 10404) afforded three oxidized metabolites 2-4. Compound 2 was found to be a new product. These metabolites were structurally characterized on the basis of modern spectroscopic techniques. Their inhibitory activity towards acetyl- and butyrylcholinesterase has been evaluated and the new product 2 has been found to be more potent than the parent compound and other metabolites.