RESUMEN
Walnut oil with very high proportion of polyunsaturated fatty acids exhibits many health beneficial effects. We hypothesized that the oil composition is led by a special pattern/mechanism for triacylglycerol (TAG) biosynthesis as well as accumulation in walnut kernel during embryo development. To test this hypothesis, shotgun lipidomics was performed for class-targeted lipid analysis (including TAG, phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid, phosphatidylglycerol, phosphatidylinositol, and lysophosphatidylcholine species) in walnut kernels from three cultivar collected at three critical stages of embryo development. The results indicated that TAG synthesis in the kernel happened before 84 days after flowering (DAF) and was significantly enhanced between 84 and 98 DAF. Moreover, TAG profile was changing along with DAFs due to the increased composition of 18:1 FA in TAG pool. Moreover, lipidomics also demonstrated that the enhanced acyl editing was responsible for the flux of FA through phosphatidylcholine for eventual TAG synthesis. Therefore, TAG biosynthesis in walnut kernel was characterized directly from lipid metabolism.
Asunto(s)
Juglans , Juglans/genética , Juglans/metabolismo , Lipidómica , Nueces/metabolismo , Ácidos Grasos Insaturados/metabolismo , Fosfatidilcolinas/metabolismo , Triglicéridos/metabolismoRESUMEN
Six undescribed macrocyclic daphnane orthoesters, stelleratenoids A-F (1-6), were isolated from the roots of Stellera chamaejasme L. Their structures were elucidated by extensive spectroscopic analyses, including HRESIMS and NMR spectra. Compound 1 features an unusual terminal double bond at C-2/C-19 in the 1α-alkyldaphnane lactone skeleton. Compounds 2-4 are unique in the presence of different long chain fatty acyl groups. Compounds 5 and 6 are unique examples of modified macrocyclic daphnane diterpenoids. All the isolates were evaluated for anti-HIV activity in MT-2 cells. Among them, compounds 1, 5 and 6 exhibited highly potent anti-HIV activity with EC50 values of 66.70, 10.62 and 55.10 nM, respectively, possessing high potential to develop new anti-HIV drugs.
Asunto(s)
Diterpenos , Thymelaeaceae , Thymelaeaceae/química , Diterpenos/química , Espectroscopía de Resonancia Magnética , Raíces de Plantas/químicaRESUMEN
In order to discover more promising anti-fungal agents, a series of benzoxazole family was synthesized by PPA-catalyzed condensation and a Raney nickel/hydrazine reduction. Altogether 45 compounds were obtained in good to excellent yields and characterized by FT-IR, NMR, MS, and X-ray crystal diffraction. Moreover, the biological activity against eight phytopathogenic fungi was investigated. All in all, most of these compounds bear moderate antifungal activities. Among them, three candidates show the strongest activities, compound 4ac, 4bc provided over 50% inhibition rate against five fungi. Especially, the inhibitory rate of compound 4ah on Mycosphaerella melonis reached 76.4%.
Asunto(s)
Antifúngicos , Benzoxazoles , Benzoxazoles/química , Relación Estructura-Actividad , Espectroscopía Infrarroja por Transformada de Fourier , Antifúngicos/química , Hongos , Pruebas de Sensibilidad Microbiana , Estructura MolecularRESUMEN
Pear is one of the most popular fruits in the world. With the fruit ripening, a series of physiological changes have taken place in fragrant pear, but up to now, the research on the metabolism and biological activity of phenolic compounds in different growth stages of fragrant pear is still lacking. In this study, four kinds of Xinjiang pears were selected as research objects, and the changes of phenolic content, antioxidant capacity, cell protection and whitening activity during fruit development were analyzed. The results showed that the phenolic content and antioxidant capacity of four pear varieties presented a decreasing trend throughout the developmental stages. The phenolic content and antioxidant activity of the four pears in the young fruit stage were the highest, and the active ingredients of the Nanguo pear were higher than the other three pear fruits. Pear extract could protect cells by eliminating excessive ROS in cells, especially in young fruit stage. The western blot results showed that the extract of fragrant pear in the young fruit stage could inhibit the expression of TYR, TYR1 and MITF in B16 cells, and it was speculated that the extract of fragrant pear in the young fruit stage might have good whitening activity. Therefore, the findings suggest that young pear display a good antioxidant potential and could have a good application prospect in food preservation and health product industry.
RESUMEN
Pear is one of the main fruits with thousands of years of cultivation history in China. There are more than 2000 varieties of pear cultivars around the world, including more than 1200 varieties or cultivars in China (Legrand et al., 2016). Xinjiang Uygur Autonomous Region is an important pear production region in China with 30 of varieties or cultivars. Pyrus sinkiangensis is the most popular variety, which is mainly distributed in Xinjiang (Zhou et al., 2018). Chlorogenic acid (CGA), p-coumaric acid, and arbutin are the main polyphenols in pear fruit, and their levels show great differences among different varieties (Li et al., 2014). CGA is a potential chemo-preventive agent, which possesses many important bioactivities including antioxidant, diabetes attenuating, and anti-obesity (Wang et al., 2021). Therefore, the specific CGA content of a variety is considered the embodiment of the functional nutritional value of pears.
Asunto(s)
Pyrus , Ácido Clorogénico , Frutas , Perfilación de la Expresión Génica , Pyrus/genética , TranscriptomaRESUMEN
Animal trypanosomiasis, caused by the members of subgenus Trypanozoon (Trypanosoma brucei brucei, T. evansi and T. equiperdum), has reduced animal productivity leading to significant negative economic impacts in endemic regions. Due to limited drug discovery and the emergence of drug-resistance over many recent decades, novel and effective compounds against animal trypanosomiasis are urgently required. This study was conducted to evaluate the antitrypanosomal potential of a batch of carbazole aminoalcohol derivatives. Among them, we found that the most effective compound was H1402, which exhibited potent trypanocidal efficacy against the bloodstream-form of T. b. brucei (EC50 = 0.73 ± 0.05 µM) and presented low cytotoxicity against two mammalian cell lines with CC50 > 30 µM. Using a murine model of acute infection, oral administration with H1402 demonstrated a complete clearance of T. b. brucei and all the infected mice were cured when they were treated twice daily for 5 days at a dose of 100 mg/kg. Furthermore, parasites were not detected in mice infected with T. evansi and T. equiperdum (the causative agents of surra and dourine, respectively, in animals) within 30 days following the same regimen with H1402. In addition, H1402 caused severe morphological and ultrastructural destruction to trypanosomes, as well as causing phosphatidylserine externalization, which are suggested to be the most likely cause of cell death. Overall, the present data demonstrated that H1402 could be promising as a rapid, safe and orally active lead compound for the development of new chemotherapeutics for animal trypanosomiasis.
Asunto(s)
Alcoholes/química , Carbazoles/química , Carbazoles/farmacología , Tripanocidas/química , Tripanocidas/farmacología , Tripanosomiasis/tratamiento farmacológico , Administración Oral , Animales , Carbazoles/administración & dosificación , Carbazoles/uso terapéutico , Ratones , Tripanocidas/administración & dosificación , Tripanocidas/uso terapéutico , Trypanosoma brucei brucei/efectos de los fármacos , Trypanosoma brucei brucei/fisiologíaRESUMEN
Starting from indole-3-acetonitrile, a total of 66 new calycanthaceous alkaloid analogues were synthesised in excellent yields. The prepared compounds were evaluated for their biological activities against a broad range of plant pathogen fungi. The results of bioassays indicated that the majority of tested compounds displayed comparable or better in vitro bioactivities than the positive control. Notably, Compound a1 displayed a significant activities against B. cereus, Escherichia sp and R. solanacearum, even better than the positive control streptomycin and Penicillin, with the same MIC value of 15.63 µg mL-1. Compound a1 displayed a broad spectrum and remarkably activities among the tested calycanthaceous analogues and might be a novel potential leading compound for further development of antifungal agents. The results obtained in the study will be very helpful for further design and structural optimisation of calycanthaceous alkaloids as potential agrochemical lead for plant disease control.
Asunto(s)
Antifúngicos/farmacología , Hongos/efectos de los fármacos , Antifúngicos/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Enfermedades de las Plantas/microbiología , Relación Estructura-ActividadRESUMEN
During our continuous efforts to pursue antifungal agents, some calycanthaceous alkaloid analogs showed diverse and promising bioactivities. Therefore, 34 new calycanthaceous alkaloid derivatives were further prepared and screened for bioactivities. As a result of the evaluation against a great deal of plant pathogen fungi, bacteria and human pathogenic fungi, a majority of them displayed potent bioactivity. In particular, compound b6 displayed remarkably activity and might be novel potential leading compound for further development of antifungal agent. The relationship between structure and biological activity was also discussed.
Asunto(s)
Alcaloides , Hongos , Alcaloides/farmacología , Antifúngicos/farmacología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-ActividadRESUMEN
The first enantioselective total synthesis of the antifungal natural product (indole-N-isoprenyl)-tryptophan-valine diketopiperazine 5 was accomplished. Four stereoisomers of 5 were intentionally prepared, and the (R, R)-isomer is more favorable in enhancing the antifungal bioactivity. Divergent structural optimization of this attractive model was conducted from the chiral pool amino acids. Fine-tuning of the structure protruded the broad-spectrum antifungal 6b, which also showed good preventative efficacy against Sclerotinia scleotiorum. Compound 5d could accelerate both hypocotyl elongation and root growth of Eclipta prostrata even at the concentration of <2.5â¯ppm. This unique and easily accessible scaffold will be of prime importance in achieving agrochemical candidates with the novel scaffold.
Asunto(s)
Productos Biológicos/uso terapéutico , Indoles/síntesis química , Productos Biológicos/farmacología , Humanos , Indoles/química , Estructura Molecular , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
Encouraged by the successful flexible modifications of the succinate dehydrogenase inhibitors, antifungal activity guided by the divergent synthesis of nicotinamides of the prevalidated pharmacophore 2-(2-oxazolinyl)aniline was conducted. The work highlighted the first utilization of the late-stage C-H functionalization assisted by the innate pharmacophore for the discovery of promising agrochemicals. New synthetic methodology and antifungal exploration of alkoxylated nicotinamides were accomplished. Fifty-five functionalized nicotinamides of 7 types were rationally designed and efficiently prepared through C-H functionalization, which facilitated the acquirement of four N-para aryloxylated nicotinamides (E3, E13, E19, and E22) as potential antifungal candidates against Botrytis cinerea, with the EC50 values lower than 5 mg/L. In vivo/vitro biotest, molecular docking, and structural analysis reconfirmed the novelty and practical potential of the antifungal candidates E3 and E19. This operationally simple platform will provide various "polar parts" and offer intriguing opportunities for the optimization of the carboxamide fungicides and structure-related pharmaceuticals.
Asunto(s)
Fungicidas Industriales/química , Niacinamida/química , Botrytis/química , Botrytis/efectos de los fármacos , Botrytis/enzimología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Proteínas Fúngicas/antagonistas & inhibidores , Proteínas Fúngicas/química , Fungicidas Industriales/farmacología , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Molecular , Niacinamida/farmacología , Enfermedades de las Plantas/microbiología , Relación Estructura-Actividad , Succinato Deshidrogenasa/antagonistas & inhibidores , Succinato Deshidrogenasa/químicaRESUMEN
Starting from 9-methyl-1,2,3,4,9,9a-hexahydro-4aH-pyrido[2,3-b]indol-4a-ol, or indole-3-acetonitrile, 40 new calycanthaceous alkaloid analogs were synthesized in excellent yields. The prepared compounds were evaluated for biological activity against acetylcholinesterase and a broad range of plant pathogen fungi. The results of bioassays indicated that the majority of tested compounds displayed comparable or better in vitro bioactivity than the positive control. Notably, compounds b8 and b9 showed higher activity against Verticillium dahlia than chlorothalonil, with MIC values of 62.5 and 7.81⯵gâ¯mL-1, respectively. Compound b3 had a higher activity against Bacillus cereus, with a MIC value of 15.63⯵gâ¯mL-1. Compounds c2 and c11 revealed potent activity against acetylcholinesterase, with MIC values of 0.01 and 0.1â¯ngâ¯mL-1, respectively. Analysis of the molecular docking modes of c2 and c11 with Torpedo californica acetylcholinesterase indicated a medium strong hydrogen bond interaction between the hydroxyl groups of both the ligands and the phenolic hydroxyl of Try121 at a distance of approximately 2.4â¯Å. The results obtained in this study will be useful for the further design and structural optimization of calycanthaceous alkaloids as potential agrochemical lead compounds for plant disease control.
Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Inhibidores de la Colinesterasa/farmacología , Alcaloides Indólicos/farmacología , Pirroles/farmacología , Acetilcolinesterasa/metabolismo , Animales , Antibacterianos/síntesis química , Antibacterianos/metabolismo , Antifúngicos/síntesis química , Antifúngicos/metabolismo , Bacterias/efectos de los fármacos , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/metabolismo , Hongos/efectos de los fármacos , Alcaloides Indólicos/síntesis química , Alcaloides Indólicos/metabolismo , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Molecular , Unión Proteica , Pirroles/síntesis química , Pirroles/metabolismo , Relación Estructura-Actividad , TorpedoRESUMEN
Three new withanolides (1-3), named as daturanolide A-C, along with six known withanolides (4-9) were isolated from the flowers of Datura metel L. Their structures with absolute configurations were elucidated by a series of spectroscopic methods, electronic circular dichroism (ECD) analyses, and X-ray crystallography. All the isolates were evaluated for cytotoxicity against five human cancer cell lines (HCT116, U87-MG, NCI-H460, BGC823, and HepG2), and 6 exhibited marked cytotoxicity.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Datura metel/química , Medicamentos Herbarios Chinos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Flores/química , Humanos , Medicina Tradicional China , Modelos Moleculares , Estructura Molecular , Relación Estructura-ActividadRESUMEN
Fischeriana A (1), a new meroterpenoid with a rare carbon skeleton, along with one of its known biosynthesis-related compounds 2,4-dihydroxy-6-methoxyacetophenone (2) and two known ent-abietane-type diterpenoids (3-4), were isolated from the roots of Euphorbia fischeriana. Their structures, including the stereochemistry, were elucidated using comprehensive spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism analysis. Compound 1 was found to be made up of an unusual heptacyclic ring system (6/6/5/5/5/6/6) featuring a modified ent-abietane diterpene with a phloroglucinol moiety. A possible biogenetic pathway for 1 was proposed. Compound 1 exhibited marked anti-tumor activities against the HepG2 cell line.
Asunto(s)
Carbono/química , Diterpenos/química , Diterpenos/farmacología , Euphorbia/química , Raíces de Plantas/química , Compuestos Policíclicos/química , Antineoplásicos/química , Antineoplásicos/farmacología , Células Hep G2 , HumanosRESUMEN
Furan ring is a key pharmacophore for insecticidal activity of limoninoids. To develop natural-product-based insecticidal agents, a series of furan-site transformations (2, 3 and 3a-j) of obacunone were synthesized by selective bromination and following coupling reactions without altering other functional groups. Bioassays indicated that derivatives 3e, 3f and 3j displayed more potent insecticidal activity than obacunone and toosendanin against the instar larvae of Mythimna separate Walker. Besides, their structure-activity relationships were discussed.
RESUMEN
Two polysaccharides JCS-1 and JCS-2 were successfully purified by DEAE-52 Cellulose chromatography from Zizyphus jujuba cv. Jinchangzao. Their structures were analyzed by high performance liquid chromatography (HPLC), high-performance gel permeation chromatography (HPGPC), nuclear magnetic resonance (NMR), and fourier transform infrared (FT-IR) spectroscopy. Further, eight sulfated derivatives are prepared by chlorosulfonic acid-pyridine (CSA-Pyr). Structural analysis revealed that both JCS-1 and JCS-2 were size uniform polysaccharides with the average molecular weight (Mw) of 71.75â¯kDa and 357.39â¯kDa, respectively. JCS-1 mainly has galacturonic acid (GalA) composition, and also contains a small amount of galactose (Gal) and arabinose (Ara), and their molar ratio is 39.04:1.26:1.39. JCS-2 was composed of GalA, mannose (Man), rhamnose (Rha), Ara and Gal, at a molar ratio of 19.87:2.07:1.77:1.65:1.16. Activity studies indicate that both natural polysaccharides and sulfated modified polysaccharides have immunomodulatory activity, while sulfated modified polysaccharides are stronger. Moreover, the sulfated polysaccharides significantly prolonged partial thromboplastin time (APTT) and thrombin time (TT) clotting times, but did not alter prothrombin time (PT) clotting time. The degree of substitution of polysaccharides seemed to be closely related to their biological characteristics. Sulfated modification represents an effective method of enhancing the immunomodulatory and anticoagulant activities of jujuba polysaccharides.
Asunto(s)
Anticoagulantes/química , Factores Inmunológicos/química , Polisacáridos/química , Ziziphus/química , Anticoagulantes/inmunología , Anticoagulantes/aislamiento & purificación , Anticoagulantes/farmacología , Arabinosa/química , Galactosa/química , Ácidos Hexurónicos/química , Humanos , Factores Inmunológicos/aislamiento & purificación , Factores Inmunológicos/farmacología , Espectroscopía de Resonancia Magnética , Manosa/química , Tiempo de Tromboplastina Parcial , Polisacáridos/inmunología , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Tiempo de Protrombina , Ramnosa/química , Espectroscopía Infrarroja por Transformada de Fourier , Sulfatos/química , Ácidos Sulfónicos/química , Tiempo de TrombinaRESUMEN
Two homogenous biological macromolecules, designated as JJC1 and JJC2 were extracted from Zizyphus jujube cv. Jinchangzao. Their molecular weights were determined to be 56.03 and 112.11kDa by high performance gel permeation chromatography (HPGPC), respectively. Chemical and spectral analysis indicated that both JJC1 and JJC2 mainly consisted of lignin, along with carbohydrates (â¼18%). Both JJC1 and JJC2 could stimulate the proliferation of spleen lymphocytes, and enhance phagocytosis and NO production of RAW264.7 cells. In addition, JJC2, but not JJC1 elicited an inhibitory effect on complement activation through the classical pathway (CH50: 2.73mg/mL) as well as the alternative pathway (AP50: 2.99mg/mL). These findings implied that water-soluble lignins were one of the bioactive components in Z. jujube, and further provided insights into the understanding of molecular basis for diverse medicinal and nutritional values of this fruit.
Asunto(s)
Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/farmacología , Proteínas del Sistema Complemento/metabolismo , Lignina/química , Lignina/farmacología , Agua/química , Ziziphus/química , Animales , Proliferación Celular/efectos de los fármacos , Activación de Complemento/efectos de los fármacos , Linfocitos/citología , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Masculino , Ratones , Fagocitosis/efectos de los fármacos , Células RAW 264.7 , Solubilidad , Bazo/citología , Bazo/efectos de los fármacosRESUMEN
A series of 21 N-protected tryptophan derivatives were synthesised from tryptophan in good yields. Their structures were characterised by IR, 1H NMR, 13C NMR, DEPT (90° and 135°) and MS analysis. The synthesised compounds were evaluated against a wide variety of plant pathogen fungi. Compounds a19 and a21 displayed activity against Fusarium oxysporum (F. oxysporum), and compound a21 showed high activity against F. oxysporum and Eggplant Verticillium, with EC50 values of 58.27 and 77.39 µg mL-1, respectively. Considering that the bioassay of the title compounds was evaluated, effects of the chain alkyl substituents may contribute to the significant variations in fungicidal potency. Their structure-antifungal activity relationships were also discussed. These results will pave the way for further design, structural modification and development of calycanthaceous alkaloids as antimicrobial agents.
Asunto(s)
Alcaloides/química , Alcaloides/farmacología , Antifúngicos/síntesis química , Antifúngicos/farmacología , Naftiridinas/química , Naftiridinas/farmacología , Triptófano/análogos & derivados , Triptófano/farmacología , Hongos/efectos de los fármacos , Fusarium/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Micelio/efectos de los fármacos , Micelio/crecimiento & desarrollo , Enfermedades de las Plantas/microbiología , Esporas Fúngicas/efectos de los fármacos , Relación Estructura-Actividad , Triptófano/síntesis química , Verticillium/efectos de los fármacosRESUMEN
A total of 29 novel tetrahydropyrroloindol-based calycanthaceous alkaloid derivatives were synthesized from indole-3-acetonitrile in good yields. The synthesized compounds were evaluated against nine strains of bacteria and a wide range of plant pathogen fungi. Bioassay results revealed that majority of the compounds displayed similar or higher in vitro antimicrobial activities than the positive control. The biological activities also indicated that substituents at R4 and R5 significantly affect the activities. Notably, compound c4 was found to be most active among the tested calycanthaceous analogues and might be a novel potential leading compound for further development as an antifungal agent. The results could pave the way for further design and structural modification of calycanthaceous alkaloids as antimicrobial agents.
Asunto(s)
Alcaloides , Antiinfecciosos , Bacterias/crecimiento & desarrollo , Fusarium/crecimiento & desarrollo , Alcaloides/síntesis química , Alcaloides/química , Alcaloides/farmacología , Antiinfecciosos/síntesis química , Antiinfecciosos/química , Antiinfecciosos/farmacologíaRESUMEN
The ß-carboline alkaloids possess a diverse range of important biochemical effects and pharmacological properties. Sixteen 3-methyl-ß-carboline derivatives were synthesized from indole formaldehyde and nitroethane via the Henry reaction, LAH/THF reduction, the Pictet-Spengler reaction and Pd/C/xylene oxidation, including four 1-substituted and twelve 9-substituted 3-methyl- ß-carboline derivatives. The structures of all the derivatives were confirmed by 1H NMR, 13C NMR and ESI-MS. Most of these 3-methyl-ß-carboline derivatives showed some antibacterial activity.
Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Carbolinas/síntesis química , Carbolinas/farmacología , Antibacterianos/química , Bacterias/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Carbolinas/química , Estructura MolecularRESUMEN
Two new sesquiterpenoids, named 2α-hydroxyxylaranol B (1) and 4ß-hydroxyxylaranol B (2), together with a known diterpenoid 3,4-seco-sonderianol (3) were isolated from the fermentation of endophytic fungus J3 of Ceriops tagal. Their structures were elucidated based on spectroscopic methods including 1D and 2D NMR (HMQC, (1)H-(1)H COSY and HMBC). All compounds were evaluated for their cytotoxic activities by MTT method, and compound 3 exhibited cytotoxic activities against K562, SGC-7901, and BEL-7402 cell lines.