RESUMO
The first phytochemical investigation of the twig extract of Uvaria leptopoda resulted in the isolation and identification of three new tetrahydroxanthene-1,3(2H)-diones, uvarialeptones A-C, two new oxidized hexadiene derivatives, uvarialeptols A and B, together with ten known compounds. Their structures were elucidated by spectroscopic techniques and mass spectrometry. Uvarialeptones A and B were unprecedented tetrahydroxanthene-1,3(2H)-dione dimers which exhibited a cyclobutane ring via [2 + 2] cycloaddition from uvarialeptone C and 9a-O-methyloxymitrone, respectively. The structure of uvarialeptone A was confirmed by X-ray diffraction analysis using Mo Kα radiation. Compound 3 inhibited NO production at an IC50 value of 6.7 ± 0.1 µM.
Assuntos
Uvaria , Uvaria/química , Estrutura Molecular , Animais , Óxido Nítrico/biossíntese , Camundongos , Xantenos/farmacologia , Xantenos/química , Cristalografia por Raios X , Oxirredução , Células RAW 264.7RESUMO
Phytochemical investigations of the twig and leaf extracts of Uvaria dac Pierre ex Finet & Gagnep. resulted in the isolation and identification of five new highly oxygenated cyclohexenes, uvaridacols M - Q (1-3, 5, and 6), and six known compounds (4 and 7-11). All new structures were elucidated by spectroscopic methods and HRESITOFMS data. The absolute configuration of 1, 5, and 6 was confirmed by single X-ray diffraction analysis with Cu Kα radiation. In contrast, other compounds were established by comparing their specific rotation and ECD spectra with those of known compounds. Some of the isolated compounds with sufficient quantity were evaluated for their α-glucosidase inhibitory activity. Of these, (-)-1,6-desoxypipoxide (10) showed α-glucosidase inhibitory activity with an IC50 value of 28.6 µM. The in silico molecular docking of active compounds was also studied.
Assuntos
Cicloexenos , Inibidores de Glicosídeo Hidrolases , Simulação de Acoplamento Molecular , Compostos Fitoquímicos , Folhas de Planta , Uvaria , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/química , Estrutura Molecular , Uvaria/química , Folhas de Planta/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Cicloexenos/isolamento & purificação , Cicloexenos/farmacologia , Cicloexenos/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Caules de Planta/química , ChinaRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer. Anomianthus dulcis (Dunal) J.Sinclair (syn. Uvaria dulcis) has been used in Thai traditional medicine in various therapeutic indications. Phytochemical constituents of A. dulcis have been isolated and identified. However, their effects on liver cancer and the associated mechanisms have not been elucidated. METHODS: Dry flowers of A. dulcis were extracted using organic solvents, and chromatographic methods were used to purify the secondary metabolites. The chemical structures of the pure compounds were elucidated by analysis of spectroscopic data. Cytotoxicity against HCC cells was examined using SRB assay, and the effects on cell proliferation were determined using flow cytometry. The mechanisms underlying HCC inhibition were examined by molecular docking and verified by Western blot analysis. RESULTS: Among 3 purified flavonoids, pinocembrin, pinostrobin, and chrysin, and 1 indole alkaloid (3-farnesylindole), only pinocembrin showed inhibitory effects on the proliferation of 2 HCC cell lines, HepG2 and Li-7, whereas chrysin showed specific toxicity to HepG2. Pinocembrin was then selected for further study. Flow cytometric analyses revealed that pinocembrin arrested the HCC cell cycle at the G1 phase with a minimal effect on cell death induction. Pinocembrin exerted the suppression of STAT3, as shown by the molecular docking on STAT3 with a better binding affinity than stattic, a known STAT3 inhibitor. Pinocembrin also suppressed STAT3 phosphorylation at both Tyr705 and Ser727. Cell cycle regulatory proteins under the modulation of STAT3, namely cyclin D1, cyclin E, CDK4, and CDK6, are substantially suppressed in their expression levels. CONCLUSION: Pinocembrin extracted from A. dulcis exerted a significant growth inhibition on HCC cells via suppressing STAT3 signaling pathways and its downstream-regulated genes.
Assuntos
Carcinoma Hepatocelular , Flavanonas , Neoplasias Hepáticas , Uvaria , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Proliferação de Células , ApoptoseRESUMO
A new oxidized heptene, 7-benzoyloxy-4-hydroxy-1-ethoxy-2E,4Z-heptadiene-1,6-dione, namely siamheptene A (1), together with eight known compounds (2-9), were isolated from the leaves of Uvaria siamensis. Their structures were elucidated by detailed analysis of spectroscopic (IR, 1D and 2D NMR) and mass spectrometric data. Compound 9 is reported for the first time from Uvaria genus. Siamheptene A was evaluated for cytotoxicity against HeLa (cervical cancer cells), A549 (lung cancer cells), and Vero cells using the MTT assay and screened for antibacterial activities. In addition, the isolated compounds (1-7, and 9) were investigated for their antioxidant (DPPH, FRAP and ABTS+ assays), anti-glycation, and anti-tyrosinase properties. Based on our results, compound 1 had mild cytotoxicity against Hela and A549 cancer cell lines, with IC50 ranging from 31.09 to 31.67â µg/mL. Compound 1 also showed antioxidant activities in all tasted assays. However, it showed no detectable activity (>128â µg/mL) against various bacterial strains, and it has no inhibitory effects on tyrosinase enzymes. Among of all tested compounds, chrysin (5), showcased highest anti-glycation and anti-tyrosinase activities. This comprehensive analysis provides highlighting the potential of 1 as a lead compound for further structural modification and development of cytotoxic or antioxidant agents.
Assuntos
Antineoplásicos , Uvaria , Animais , Chlorocebus aethiops , Humanos , Monofenol Mono-Oxigenase , Uvaria/química , Antioxidantes/farmacologia , Antioxidantes/química , Células Vero , Antineoplásicos/farmacologia , Extratos Vegetais/químicaRESUMO
The use of medicinal plants as food and medicine has been a common practice in the world, especially in tropical African countries. One such plant in West Africa is Uvaria chamae, also known as Bush banana, renowned for its diverse ethnomedicinal applications and, more recently, for its pharmacological activities attributed to a rich array of phytochemical constituents. Various parts of the plant have been traditionally employed for the treatment of diverse health issues such as digestive disorders, fever, dysmenorrhea, cancer, wound healing, and many more. To unravel the bioactive compounds responsible for these medicinal properties, a comprehensive phytochemical analysis has been undertaken. Notable isolates include chamanetin, dichamanetin, uvaretin, and uvarinol from different parts of the plant. The pharmacological evaluation of these compounds has revealed significant anticancer and antimicrobial properties. Therefore, this review provides a thorough examination of the phytochemicals derived from Uvaria chamae, detailing their associated pharmacological activities both in vitro and in vivo. The review emphasizes the potential of Uvaria chamae as a valuable source of lead compounds for cancer chemotherapy and antimicrobial drug discovery.
Assuntos
Medicina Tradicional , Compostos Fitoquímicos , Uvaria , Humanos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Animais , Uvaria/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Fitoterapia , Plantas Medicinais/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/isolamento & purificaçãoRESUMO
Four new adjacent bis-tetrahydrofuran acetogenins, bullacin C (7), uvarirufin (9), and uvariasolins III (12) and IV (13), along with 11 known acetogenins, were isolated from the stem of Uvaria rufa. Their structures were elucidated based on spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, and MALDI-MS/MS of the lithium adducts. Absolute configurations were assigned using Mosher ester analysis and ECD measurements. Uvarirufin (9) possesses a unique C-39 skeleton among acetogenins. Most tested acetogenins exhibited cytotoxicity against human cancer cell lines (HCT 116, 22Rv1, MDA-MB-435, OVCAR3). Squamocin (8) and uvarirufin (9) were found to be the most potent, with an IC50 value of 1.2 µM for both in HCT 116 colon cancer cells. Additionally, a new application of Dragendorff's reagent is proposed herein for the TLC detection of acetogenins.
Assuntos
Antineoplásicos , Neoplasias Ovarianas , Uvaria , Feminino , Humanos , Acetogeninas/farmacologia , Acetogeninas/química , Apoptose , Linhagem Celular Tumoral , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrometria de Massas em Tandem , Uvaria/químicaRESUMO
Six undescribed compounds, uvarirufols D and E, (+)-uvarigranol B, (-)-uvarigranol E, 6-acetoxy-5-hydroxy-7-methoxyflavanone and cherrevenaphthalene D, along with twelve known compounds, including polyoxygenated cyclohexenes, flavonoids, and lignans, were isolated from the methanol extract of Uvaria rufa stems. Their structures were elucidated by spectroscopic analyses and the absolute configurations were determined using electronic circular dichroism. Several isolates were evaluated for cytotoxic, antitubercular and anti-inflammatory potentials. (-)-6-Acetylzeylenol showed moderate inhibitory activity against Mycobacterium tuberculosis, with MIC value of 47.10 µg/mL. Cherrevenaphthalene D exhibited weak antimycobacterial activity and potent inhibitory effect on lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 cells (EC50 = 8.54 µM). 8-Hydroxy-5,7-dimethoxyflavanone displayed moderate level of NO inhibition (EC50 = 43.62 µM) with little cytotoxicity. The polyoxygenated cyclohexenes and lignans were inactive against HCT 116 and 22Rv1 cancer cells (IC50 > 100 µM).
Assuntos
Lignanas , Uvaria , Uvaria/química , Estrutura Molecular , Cicloexenos/farmacologia , Cicloexenos/química , Lignanas/farmacologiaRESUMO
The leaf oil compositions of two Lauraceae and one Annonaceae plants cultivated in Vietnam were analysed by GC/MS (gas chromatography-mass spectrometry) analysis. The leaf oil of the first Lauraceae plant Cinnamomum melastomaceum contained 34 identified compounds, in which benzyl benzoate (38.5 %), linalool (19.9 %), (E)-caryophyllene (10.5 %), and α-terpineol (6.9 %) were the major compounds. The leaves of the second Lauraceae plant Neolitsea buisanensis gave an oil with the main compounds (E)-ß-ocimene (24.0 %), benzyl benzoate (15.8 %), bicyclogermacrene (14.9 %), and (E)-caryophyllene (6.3 %). The leaf oil of the Annonaceae plant Uvaria microcarpa consisted of the principal compounds (E)-caryophyllene (18.0 %), bicyclogermacrene (8.1 %), and δ-elemene (6.1 %). Two Lauraceae oil samples exhibited strong mosquito larvicidal activity against Aedes aegypti, Ae.â albopictus, and Culex quinquefasciatus with LC50 and LD90 values of less than 50â µg/mL. The Annonaceae oil sample showed strong antimicrobial activity against the fungus Aspergillus niger ATCC 1015 with the MIC (minimum inhibitory concentration) value of 32â µg/mL. In the docking approach, the major compounds (E)-caryophyllene, bicyclogermacrene, and benzyl benzoate interacted with the mosquito odorant-binding protein 3OGN, whereas (E)-caryophyllene, bicyclogermacrene, and δ-elemene also potentially interacted with the 4ZA5 protein of fungus A.â niger.
Assuntos
Aedes , Anti-Infecciosos , Cinnamomum , Inseticidas , Lauraceae , Óleos Voláteis , Uvaria , Animais , Óleos Voláteis/química , Simulação de Acoplamento Molecular , Vietnã , Anti-Infecciosos/farmacologia , Anti-Infecciosos/análise , Inseticidas/química , Larva , Folhas de Planta/químicaRESUMO
The present study was carried out to investigate the anti-inflammatory activity of a methanolic extract and fractions of Uvaria comperei stems. The crude extract was obtained by maceration of the powder in methanol and fractions by vacuum chromatography from the methanolic extract. To study the anti-inflammatory activity in vitro, red blood cell lysis inhibition assay and albumin denaturation inhibition were performed, while in vivo measurements of carrageenan-induced paw oedema and formalin-induced pain in albino mice were performed. Acute toxicity and cytotoxicity studies of the fraction F2 were performed, as well as its HPLC, and some biochemical parameters were quantified. Uvaria comperei crude extract (UCCE) at 250 and 500 µg/mL completely inhibited albumin denaturation, while decreasing 75.5% of heat blood cell lysis at 500 µg/mL. The fractions 128-136 (F3), 10-11 (F1), and 56-62 (F2) at 500 µg/mL displayed a significant anti-inflammatory activity with percentages of inhibition of 60.5, 67.4, and 100%, respectively. Administration of fraction F2 (25, 50, and 100 mg/kg, p.o.) produced a dose-dependent inhibition of formalin-induced pain of 60.2% at 50 mg/kg in the neurogenic phase (p < 0.05) and 70.2% at 25 mg/kg in the inflammatory phase (p < 0.05). Similarly, the time-dependent increase in carrageenan-induced paw circumference induced by carrageenan was inhibited by pretreatment with F2: 50% of inhibition at 25 mg/kg after 30 min (p < 0.05) and 96.5% inhibition at 25 mg/kg after 6 h (p < 0.05). In this research, the fraction F2 presented its maximum analgesic property at 50 mg/kg, while it presented the highest anti-inflammatory property at 25 mg/kg. The oral lethal median dose (LD50) of F2 was determined to be greater than 2000 mg/kg; further low cytotoxicity in RAW cells was also observed. Overall, this work shows that the methanolic crude extract and fractions, mainly F2, of Uvaria comperei stem have interesting anti-inflammatory properties.
Assuntos
Uvaria , Animais , Camundongos , Carragenina/efeitos adversos , Extratos Vegetais/química , Anti-Inflamatórios/uso terapêutico , Analgésicos , Dor/tratamento farmacológico , Metanol , Edema/induzido quimicamente , Edema/tratamento farmacológicoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Streptococcus mutans a key pathogen, produces biofilm, acids and extracellular polysaccharides in the oral cavity; which leads to the development of dental caries. Control of these pathogenic markers can prevent dental caries. Uvaria chamae P. Beauv. is a medicinal plant traditionally used for many ailments including oral infections. Root, leaves and bark extracts has proven antibacterial activity including activity against caries causing S. mutans. However, its effect on the virulence properties of S. mutans, responsible for the development of dental caries, has not been studied. AIM OF THE STUDY: This study investigated the phytochemical constituents, anti-S. mutans, anti-adherence and anti-acidogenic activity of U. chamae root extract. MATERIALS AND METHODS: Extracts were prepared and phytochemical analysis was performed. Minimum inhibitory concentrations (MIC) were determined, and MIC and sub-MIC concentrations of the best solvent were selected for their effect on the virulence factors of S. mutans. The results were analysed using one-way ANOVA and Wilcoxon Rank Sum Tests. RESULTS: The dichloromethane extract, with proanthocyanidin as a major chemical constituent, produced an MIC of 0.02 mg/ml. At 6 h, exposure to 0.005, 0.01, and 0.02 mg/ml extract significantly reduced S. mutans adherence by 39, 59, and 77% respectively (p < 0.05). Uvaria chamae also significantly inhibited acid production in S. mutans at 10, 12, 14 and 16 h (p < 0.05). At ½ MIC, the plant extract caused remarkable downregulation of the virulence genes responsible for the adherence, biofilm formation, extracellular polysaccharide synthesis and acid production. CONCLUSIONS: This suggests that U. chamae extract may potentially be used to inhibit the proliferation of S. mutans and silencing the expression of pathology-related genes, which will prevent the development of dental caries.
Assuntos
Cárie Dentária , Proantocianidinas , Uvaria , Ácidos , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes , Cárie Dentária/prevenção & controle , Cloreto de Metileno/farmacologia , Testes de Sensibilidade Microbiana , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Solventes/farmacologia , Streptococcus mutans , Uvaria/química , Fatores de VirulênciaRESUMO
Background: The objective of this study was to evaluate the anti-inflammatory activities and phytochemical composition of the leaves extracts of Boscia coriacea Graells and Uvaria leptocladon Oliv. Methods: The powdered leaves of Boscia coriacea Graells and Uvaria leptocladon Oliv were extracted by maceration and soxhlet extraction methods. Anti-inflammatory activity of the leaves extracts of Boscia coriacea Graells and Uvaria leptocladon Oliv were evaluated using carrageenan-induced paw edema model. Standard methods were used for analysis of phytochemical composition of the leaves extracts of Boscia coriacea Graells and Uvaria leptocladon Oliv. Data analysis was done using one way analysis of variance. Results: U. leptocladon Oliv (200 mg/kg) and B. coriacea Graells (200 mg/kg) showed percent inhibition on mice paw edema of 86% and 75% after six hours of carrageenan injection, respectively. The ethanol fraction (100 mg/kg) of U. leptocladon Oliv showed the highest anti-inflammatory effect after six hours of carrageenan injection. The phytochemical analysis of the leaves extracts of B. coriacea and U. leptocladon revealed the presence of tannins, alkaloids, cardiac glycoside, flavonoids, phenols, quinones, and saponins. Conclusion: The crude leaves extracts of B. coriacea Graells and U. leptocladon Oliv contain phytochemicals with anti-inflammatory activities.
Assuntos
Uvaria , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Carragenina/efeitos adversos , Carragenina/análise , Edema/tratamento farmacológico , Camundongos , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta , Uvaria/químicaRESUMO
Background: The objective of this study was to evaluate the in vivo toxicity and antibacterial activity of the leaves extracts of Boscia coriacea and Uvaria leptocladon. Methods: Extraction was performed using 80% methanol by maceration and Soxhlet extraction method. Evaluation of the acute toxicity of the extracts was based on the Organization for Economic Cooperation and Development (OECD) guideline. Evaluation of antibacterial activity of the extracts was done by agar well diffusion assay. Determinations of minimum inhibitory concentrations (MIC) of the extracts were performed by broth macro-dilution method. The checkerboard method was used for the determination of combined effect of antibiotics and the extracts. Paired T-test and one way analysis of variance were used for statistical analysis. Results: B. coriacea and U. leptocladon have no toxic effect in Swiss albino mice up to dose of 5000 mg/kg. B. coriacea and U. leptocladon showed antibacterial activity at concentration of 500 mg/ml. The chloroform-methanol fraction of B. coriacea and U. leptocladon showed the highest antibacterial activity at concentration of 25 mg/ml. The MIC and minimum bactericidal concentration (MBC) of B. coriacea were 125 mg/ml and 250 mg/ml, respectively. The MIC of U. leptocladon ranged from 31.25 mg/ml to 62.5 mg/ml, while its MBC ranged from 62.5 to 125 mg/ml. The combination assay of B. coriacea and the antibiotics showed additive effect, while U. leptocladon and the antibiotics showed indifferent effect. Conclusion: The findings showed that U. leptocladon and B. coriacea leaves extracts have antibacterial activity and no toxicity in animal model.
Assuntos
Uvaria , Animais , Antibacterianos/toxicidade , Metanol , Camundongos , Testes de Sensibilidade Microbiana , Extratos Vegetais/toxicidade , Folhas de PlantaRESUMO
Dulcisenes C-E, undescribed polyoxygenated cyclohexenes and twenty-one known compounds were isolated from the dichloromethane extract of the leaves of Uvaria dulcis Dunal. The structures of these undescribed compounds were determined by spectroscopic data analyses, including 1D and 2D NMR, IR, and MS techniques; their absolute configurations were analyzed by NOESY and ECD spectra. Cytotoxicity of sixteen more abundant isolates was evaluated. Cherrevenone and 2',3'-dihydroxy-4',6'-dimethoxychalcone exhibited cytotoxic activity against some cancer cell lines with IC50 values in the range of 3.3-11.8 µM.
Assuntos
Antineoplásicos Fitogênicos , Antineoplásicos , Uvaria , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cicloexenos/química , Estrutura Molecular , Folhas de Planta/química , Uvaria/químicaRESUMO
Three new oxygenated cyclohexene derivatives, pandensenol D - F (1-3), two new flavanoids, pandensone A and B (4-5), and seven known compounds (6-12) were isolated from the methanol extract of the leaves of Uvaria pandensis Verdc. (Annonaceae). The structures were characterized by NMR spectroscopic and mass spectrometric analyses. The isolated metabolites were evaluated for their antibacterial activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus epidermidis, the Gram-negative bacteria Enterococcus raffinosus, Escherichia coli, Paraburkholderia caledonica, Pectobacterium carotovorum and Pseudomonas putida, and for cytotoxicity against the MCF-7 human breast cancer cell line. Out of the tested compounds, pandensenol D (1) and (6',7'-dihydro-8'α,9'ß-dihydroxy)-3-farnesylindole (12) showed weak activity, whereas (8'α,9'ß-dihydroxy)-3-farnesylindole (11) strong activity against B. subtilis. Four of the isolated compounds (1, 4, 11 and 12) showed moderate cytotoxicity against MCF-7 breast cancer cells (EC50 > 100 µM).
Assuntos
Uvaria , Antibacterianos/farmacologia , Bacillus subtilis , Cicloexenos , Flavonoides/análise , Flavonoides/farmacologia , Humanos , Estrutura Molecular , Folhas de Planta/química , Uvaria/químicaRESUMO
A new C-benzylated flavone, uvariaruflavone (1), along with 13 known compounds (2-14) were isolated from the twig and leaf extracts of Uvaria rufa Blume. Their structures were established by extensive spectroscopic methods. Flavones (5-8) and cyclohexene (10) were isolated from U. rufa for the first time. Most of the isolated compounds were evaluated for their α-glucosidase and α-amylase inhibitory activities. Of these, uvariaruflavone (1) showed the highest α-glucosidase inhibitory activity with an IC50 value of 44.3 µM, while ferrudiol (12) displayed the highest α-amylase inhibitory activity with an IC50 value of 73.5 µM.
Assuntos
Uvaria , Uvaria/química , alfa-Glucosidases , Inibidores de Glicosídeo Hidrolases/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , alfa-AmilasesRESUMO
Phytochemical investigation applying GC (gas chromatography)-MS (mass spectrometry)/GC-FID (flame ionization detection) on the hydro-distilled essential oils of the Vietnamese medicinal plant Uvaria boniana leaf and twig lead to the detection of 35 constituents (97.36%) in the leaf oil and 52 constituents (98.75%) in the twig oil. Monoterpenes, monoterpenoids, sesquiterpenes, and sesquiterpenoids were characteristic of U. boniana essential oils. The leaf oil was represented by major components (E)-caryophyllene (16.90%), bicyclogermacrene (15.95%), α-humulene (14.96%), and linalool (12.40%), whereas four compounds α-cadinol (16.16%), epi-α-muurolol (10.19%), α-pinene (11.01%), and ß-pinene (8.08%) were the main ones in the twig oil. As compared with the leaf oil, the twig oil was better in antimicrobial activity. With the same MIC value of 40 mg/mL, the twig oil successfully controlled the growth of Gram (+) bacterium Bacillus subtilis, Gram (-) bacterium Escherichia coli, fungus Aspergillus niger, and yeast Saccharomyces cerevisiae. In addition, both two oil samples have induced antiinflammatory activity with the IC50 values of 223.7-240.6 mg/mL in NO productive inhibition when BV2 cells had been stimulated by LPS. Docking simulations of four major compounds of U. boniana twig oil on eight relevant antibacterial targets revealed that epi-α-muurolol and α-cadinol are moderate inhibitors of E. coli DNA gyrase subunit B, penicillin binding protein 2X and penicillin binding protein 3 of Pseudomonas aeruginosa with similar free binding energies of -30.1, -29.3, and -29.3 kJ/mol, respectively. Furthermore, in silico ADMET studies indicated that all four docked compounds have acceptable oral absorption, low metabolism, and appropriated toxicological profile to be considered further as drug candidates.
Assuntos
Óleos Voláteis , Sesquiterpenos , Uvaria , Escherichia coli , Cromatografia Gasosa-Espectrometria de Massas , Óleos Voláteis/química , Folhas de Planta/química , Óleos de Plantas/análise , Sesquiterpenos/análise , Sesquiterpenos/farmacologiaRESUMO
The genus Uvaria (Annonaceae) comprises of climbing or trailing shrubs and rarely trees. Its plant species are widely distributed across tropical Africa, Asia and Australia. The genus Uvaria is known for various ethnobotanical uses including the treatment of tumours and the control of fever. Some of plant species in this genus have been studied for their ethnobotanical uses, biological activities and phytochemistry. The aim of the present study is to give a comprehensive review of plant species from the genus Uvaria in terms of their ethnobotanical uses, biological activities and phytochemistry. This review is expected to lay a foundation for further studies of this genus in terms of ethnobotanical applicability, biological activities and phytochemistry. Since many compounds currently known from the genus Uvaria have not yet been investigated for their biological activities, this review will be useful for future studies in the phytochemical investigations of lead compounds from this genus.
Assuntos
Uvaria , Etnobotânica , Etnofarmacologia , Compostos Fitoquímicos/farmacologia , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
Five new cyclohexene derivatives, dipandensin A and B (1 and 2) and pandensenols A-C (3-5), and 16 known secondary metabolites (6-21) were isolated from the methanol-soluble extracts of the stem and root barks of Uvaria pandensis. The structures were characterized by NMR spectroscopic and mass spectrometric analyses, and that of 6-methoxyzeylenol (6) was further confirmed by single-crystal X-ray crystallography, which also established its absolute configuration. The isolated metabolites were evaluated for antibacterial activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus epidermidis and the Gram-negative bacteria Enterococcus raffinosus, Escherichia coli, Paraburkholderia caledonica, Pectobacterium carotovorum, and Pseudomonas putida, as well as for cytotoxicity against the MCF-7 human breast cancer cell line. A mixture of uvaretin (20) and isouvaretin (21) exhibited significant antibacterial activity against B. subtilis (EC50 8.7 µM) and S. epidermidis (IC50 7.9 µM). (8'α,9'ß-Dihydroxy)-3-farnesylindole (12) showed strong inhibitory activity (EC50 9.8 µM) against B. subtilis, comparable to the clinical reference ampicillin (EC50 17.9 µM). None of the compounds showed relevant cytotoxicity against the MCF-7 human breast cancer cell line.
Assuntos
Cicloexenos/química , Oxigênio/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Caules de Planta/química , Uvaria/química , Cristalografia por Raios X/métodos , Cicloexenos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Células MCF-7 , Testes de Sensibilidade Microbiana , Extratos Vegetais/químicaRESUMO
BACKGROUND: Uvaria chamae (UC) and Olax subscorpioidea (OS) roots are included in traditional anti-cancer remedies and some studies have identified their chemopreventive/chemotherapeutic potential. This study aimed to identify some cellular/molecular mechanisms underlying such potential and the associated chemical constituents. METHODS: Effect on the viability of cancer cells was assessed using the Alamar Blue assay; ability to modulate oxidative stress was assessed using the 2',7'-dichlorofluorescein diacetate (DCFDA) assay; potential to modulate Nuclear factor erythroid 2-related factor like-2 (Nrf2) activity was assessed in the AREc32 luciferase reporter cell line; and anti-inflammatory effect was assessed using lipopolysaccharide-induced nitric oxide release model in the RAW264.7 cells (Griess Assay). Chemical constituents were identified through liquid chromatography-mass spectrometry (LC-MS). RESULTS: Extracts up to 100 µg/ml were non-toxic or mildly toxic to HeLa, AREc32, PC3 and A549 cells (IC50 > 200 µg/ml). Each extract reduced basal and peroxide-induced levels of reactive oxygen species (ROS) in HeLa cells. OS and UC activated Nrf2, with UC producing nearly four-fold induction. Both extracts demonstrated anti-inflammatory effects. Chamanetin, isochamanetin, isouvaretin, uvaricin I and other compounds were found in U. chamae root extract. CONCLUSION: As Nrf-2 induction, antioxidant and anti-inflammatory activities are closely linked with chemoprevention and chemotherapy of cancers, the roles of these plants in traditional anti-cancer remedies are further highlighted, as is their potential as sources of drug leads.
Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Neoplasias/tratamento farmacológico , Olacaceae/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Uvaria/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Fatores de Transcrição de Zíper de Leucina Básica/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas/efeitos dos fármacos , Doxorrubicina/uso terapêutico , Humanos , Extratos Vegetais/química , Raízes de Plantas/química , Plantas Medicinais/química , Streptomyces/químicaRESUMO
Natural products--polyoxygenated cyclohexenes exhibited potent anti-tumor activity, such as zeylenone, which is a natural product isolated from Uvaria grandiflora Roxb. This article will attempt to establish a gram-scale synthesis method of (+)-zeylenone and explain the structure-activity relationship of this kind of compound. Total synthesis of (+)-zeylenone was completed in 13 steps with quinic acid as the starting material in 9.8% overall yield. The highlight of the route was the control of the three carbon's chirality by single step dihydroxylation. In addition, different kinds of derivatives were designed and synthesized. Cell Counting Kit-8 (CCK8) assay was used for evaluating antitumor activity against three human cancer cell lines. The structure--activity relationship suggested that compounds with both absolute configurations exhibited tumor-suppressive effects. Moreover, hydroxyls at the C-1/C-2 position were crucial to the activity, and the esterification of large groups at C-1 hydroxyl eliminated the activity. Hydroxyl at the C-3 position was also important as proper ester substituent could increase the potency.