RESUMEN
In research related to fungicides, the development of compounds from natural products with high antifungal activity has attracted considerable attention. Fusaric acid (FA), an alkaloid isolated from the metabolites of Fusarium oxysporum, is an important precursor for developing pharmacologically active herbicides. In our previous work, we reported that FA has a wide range of inhibitory activities against 14 plant pathogenic fungi. In particular, it exhibited excellent antifugal effects on Colletotrichum higginsianum (EC50 = 31.7 µg/mL). Herein, to explore the practical application in the agricultural field, the design and synthesis of three series of FA derivatives and their inhibitory activities against plant pathogenic fungi were examined. Results demonstrated that the optimized FA derivatives had excellent inhibitory activities against C. higginsianum, Helminthosporium (Harpophora maydis), and Pyricularia grisea. In particular, the inhibitory activities were considerably improved when the 5-butyl groups of FA were substituted. The EC50 of C. higginsianum and P. grisea was only 1.2 and 12.0 µg/mL when 5-butylalkyl groups were substituted with 5-([1,1'-biphenyl]-4-yl) and 5-phenyl, respectively. Moreover, the safety index of target compounds, which was obtained from the treatment index of medicines, on rice seeds was evaluated. Finally, 16 leading compounds (H4, H22-H24, H27, H29, H30-H34, H37, H45, H50, H52, and H53) were obtained; they had considerable potential for additional modification and optimization as agricultural fungicides. Moreover, three-dimensional quantitative structure-activity relationship models were developed for obtaining a systematic structure-activity relationship profile to explore the possibility of more potent FA derivatives as novel fungicides.
Asunto(s)
Fungicidas Industriales , Fusarium , Fungicidas Industriales/farmacología , Relación Estructura-Actividad Cuantitativa , Relación Estructura-Actividad , Antifúngicos/farmacología , Pyricularia griseaRESUMEN
Nitrile imines are highly reactive and versatile dipoles and conventionally generated in situ from unstable hydrazonyl halides under basic conditions. Herein, we report the first green and user-friendly protocol for in situ generation of nitrile imines from Oxone-KBr oxidation of hydrazones and base-promoted dehydrobromination. The nitrile imines were demonstrated for 1,3-dipolar cycloaddition with various dipolarophiles, including alkene and alkyne groups. With its green nature, ease of operation, and air and moisture tolerance, we expect our method will find wide applications in organic synthesis.
Asunto(s)
Iminas , Nitrilos , Reacción de Cicloadición , Hidrazonas , Estructura MolecularRESUMEN
The acyclic organic alkynes and carbyne bonds exhibit linear shapes. Metallabenzynes and metallapentalynes are six- or five-membered metallacycles containing carbynes, whose carbine-carbon bond angles are less than 180°. Such distortion results in considerable ring strain, resulting in the unprecedented reactivity compared with acyclic carbynes. Meanwhile, the aromaticity of these metallacycles would stabilize the ring system. The fascinating combination of ring strain and aromaticity would lead to interesting reactivities. This mini review summarized recent findings on the reactivity of the metal-carbon triple bonds and the aromatic ring system. In the case of metallabenzynes, aromaticity would prevail over ring strain. The reactions are similar to those of organic aromatics, especially in electrophilic reactions. Meanwhile, fragmentation of metallacarbynes might be observed via migratory insertion if the aromaticity of metallacarbynes is strongly affected. In the case of metallapentalynes, the extremely small bond angle would result in high reactivity of the carbyne moiety, which would undergo typical reactions for organic alkynes, including interaction with coinage metal complexes, electrophilic reactions, nucleophilic reactions and cycloaddition reactions, whereas the strong aromaticity ensured the integrity of the bicyclic framework of metallapentalynes throughout all reported reaction conditions.
Asunto(s)
Carbamatos/química , Carbamatos/síntesis química , Reacción de CicloadiciónRESUMEN
The total synthesis of a natural product alkaloid fusaric acid (FA), which exhibits herbicide, fungicide, insecticide and even diverse notable pharmacological activities, was accomplished in four steps using commercially available materials. The synthesis, based on a unified and flexible strategy using 6-bromonicotinaldehyde as a common intermediate, is concise, convergent, practical and can be carried out on a two-gram scale. This approach could be readily applicable to the synthesis of its analogues. In addition, FA had a wide range of inhibitory activities against 14 plant pathogenic fungi in this study, which demonstrated that as a leading compound, and it has great potential to be further developed as an agricultural fungicide.
Asunto(s)
Antifúngicos , Hongos/crecimiento & desarrollo , Ácido Fusárico , Enfermedades de las Plantas/microbiología , Antifúngicos/síntesis química , Antifúngicos/química , Antifúngicos/farmacología , Ácido Fusárico/síntesis química , Ácido Fusárico/química , Ácido Fusárico/farmacologíaRESUMEN
A new cascade approach has been developed for the one-pot four-step divergent synthesis of polysubstituted benzofurans and 2H-chromenes, featuring a novel cascade aromatic Claisen rearrangement/Meinwald rearrangement/dehydrative or oxidative cyclization. This new method was demonstrated with 39 examples tolerating different substitutions at an epoxide, allylic ether, and aromatic ring, and we showcased its utility with the first total synthesis of natural product liparacid A in seven steps.
RESUMEN
The total synthesis of potent anti-obesity lansiumamide B was accomplished in four steps using commercially available materials. The synthetic strategy, featured with copper-catalyzed Buchwald coupling, is concise, convergent, practical and can be carried out on a one-gram scale. This approach could give either Z- or E-configured enamide moiety in natural products with absolute stereocontrol and was applied in the total synthesis of natural products.
Asunto(s)
Fármacos Antiobesidad/síntesis química , Productos Biológicos/síntesis química , Cinamatos/síntesis química , Fármacos Antiobesidad/química , Productos Biológicos/química , Catálisis , Cinamatos/química , Estructura Molecular , EstereoisomerismoRESUMEN
A efficient 2-step protocol has been applied for the synthesis of Lansiumamide B (N-methyl-N-cis-styryl-cinnamamide, 2) derivatives by various substitution on the amide nitrogen with alkyl, allyl, propargyl, benzyl or ester groups. The structures of nine new compounds were characterized by HRMS, ¹H NMR, and 13C NMR spectra. These compounds were tested in vitro against 10 strains of phytopathogenic fungi and showed a wide antifungal spectrum. The relationship between different substituents on the amide nitrogen and antifungal activity of Lansiumamide B derivatives were compared and analyzed. The result indicates that the length and steric hindrance of N-substitution have a significant impact on biological activities. It is noteworthy that the methyl or ethyl substituent on the amide nitrogen is critical for the antifungal activities.
Asunto(s)
Botrytis/efectos de los fármacos , Cinamatos/síntesis química , Fungicidas Industriales/síntesis química , Estirenos/síntesis química , Alquilación , Ascomicetos/efectos de los fármacos , Ascomicetos/crecimiento & desarrollo , Botrytis/crecimiento & desarrollo , Cinamatos/farmacología , Ésteres , Fungicidas Industriales/farmacología , Fusarium/efectos de los fármacos , Fusarium/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Phytophthora/efectos de los fármacos , Phytophthora/crecimiento & desarrollo , Relación Estructura-Actividad , Estirenos/farmacologíaRESUMEN
In this paper, we investigated the chemical components of the flowers of Cymbidium Lunagrad Eternal Green for the first time. In the whole post-fertilization, a new alkaloid, named Lunagrad A (1), and a new aromatic glucoside, named Lunagrad B (2), were isolated from the MeOH extract of the flowers of Cymbidium Lunagrad Eternal Green, along with other six known aromatic compounds (3-8) and three flavone glucosides (9-11). These structures were determined on the basis of NMR experiments, as well as chemical evidence.
Asunto(s)
Alcaloides/química , Flores/química , Glucósidos/química , Orchidaceae/química , Alcaloides/aislamiento & purificación , Arbutina/química , Arbutina/aislamiento & purificación , Alcoholes Bencílicos/química , Alcoholes Bencílicos/aislamiento & purificación , Flavonoides/química , Flavonoides/aislamiento & purificación , Glucósidos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Estructura Molecular , Extractos Vegetales/químicaRESUMEN
Triterpenoids possess a wide range of biological effects. Here, the cytotoxic activities of 55 triterpenes and derived glycosides against BEL-7404 and SGC-7901 cells were assessed, and structure-activity relationships were analysed accordingly. Nine of them effectively inhibited the two cell lines. In particular, compounds 49 and 52 inhibited BEL-7404 cells as efficiently as 5'-fluorouracil (IC50 values 0.46 and 1.48, respectively). Moreover, we found that compounds 49 and 52 induced apoptosis in BEL-7404 cells. Indeed, DNA fragmentation assay showed a time-dependent degradation of DNA after treatment of cells with compounds 49 and 52. In addition, Bax gene expression levels were increased after treatment with these compounds, in a concentration-dependent manner. Taken together, our findings suggested that compounds 49 and 52 induce apoptosis in BEL-7404 cells by upregulating the Bax gene without affecting Bcl-2 gene expression.
Asunto(s)
Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Glicósidos/farmacología , Relación Estructura-Actividad , Triterpenos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Fragmentación del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glicósidos/química , Humanos , Concentración 50 Inhibidora , Proteínas Proto-Oncogénicas c-bcl-2/genética , Triterpenos/química , Proteína X Asociada a bcl-2/genéticaRESUMEN
A new approach has been developed for the synthesis of 8-substituted 2H-chromenes, featuring a novel cascade aromatic Claisen rearrangement/o-quinone methide formation/6π-electrocyclization. This new method was demonstrated with 28 examples tolerating different substitutions at alkenes, allylic and aromatic ring and with total syntheses of three 2H-chromene natural products.
RESUMEN
Five new taraxerene-type triterpenes, 2-nor-D-friedoolean-14-en-28-ol (1), 2-nor-d-friedoolean-14-en-3α,28-diol (2), 6α-hydroxy-2-nor-D-friedoolean-14-en-3,21-dione (3), 6α,11α,29-trihydroxy-D-friedoolean-14-en-3,16,21-trione (4), and 6α,23,29-trihydroxy-D-friedoolean-14-en-3,16,21-trione (5), were isolated from the MeOH extract of the branch barks of Davidia involucrata, together with five known compounds. Their structures were elucidated by means of various spectroscopic analyses. Five of the identified compounds showed moderate cytotoxicities against the cell proliferation of SGC-7901, MCF-7, and BEL-7404.
Asunto(s)
Antineoplásicos Fitogénicos/química , Cornaceae/química , Triterpenos/química , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Humanos , Células MCF-7 , Estructura Molecular , Análisis Espectral/métodos , Triterpenos/farmacologíaRESUMEN
Three new ursane triterpenes, 3α,19α-dihydroxy-2-nor-urs-12-en-23,28-dioic acid-23-methyl ester (1), 19α,23-dihydroxy-3-oxo-2-nor-urs-12-en-28-oic acid (2), and 2,3-seco-3-methoxy-3,19α,23-trihydroxy-urs-12-en-2-al-28-oic acid (3), were isolated from the MeOH extract of the branch barks of Davidia involucrata, together with six known compounds. Their structures were elucidated by means of various spectroscopic analyses. The isolated triterpenes provide important evolutionary and chemotaxonomic knowledge about the monotypic genus Davidia. Five of the identified compounds showed moderate cytotoxicities against the cell proliferation of SGC-7901, MCF-7, and BEL-7404 with IC50 range from 7.26 to 47.41 µM.
Asunto(s)
Antineoplásicos Fitogénicos/química , Asteraceae/química , Corteza de la Planta/química , Extractos Vegetales/química , Triterpenos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Evolución Biológica , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Estructura Molecular , Filogenia , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Triterpenos/aislamiento & purificación , Triterpenos/farmacologíaRESUMEN
Ligustrum sinense are commonly used for their anti-inflammatory, anti-rheumatic, diuretic, and hypotensive activities in traditional Chinese medicine. To observe the effects of the combined treatment of a water-soluble extract of Ligustrum sinense (WEL) and gentamicin sulphate (GS) on Pseudomonas aeruginosa PA01, the micro-dilution method was used to determine the minimal inhibitory concentration (MIC) of GS. Formation of a PA01 biofilm was observed under an optical microscope after treatment with different dosages of WEL and combined treatment with GS. The MIC of WEL was 8g l(-1), and permanent activity was also observed. The effect of WEL with GS was synergistic. The motility, biomass of biofilms, and production of pyocyanin of P. aeruginosa were strongly suppressed in the presence of WEL. The conclusion can be drawn that combined antibiotics can be used to treat the contamination due to the biofilm formation caused by P. aeruginosa.
Asunto(s)
Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Gentamicinas/farmacología , Ligustrum/química , Pseudomonas aeruginosa/fisiología , Antibacterianos/química , Farmacorresistencia Bacteriana , Extractos Vegetales , Agua/químicaRESUMEN
A new seco-neolignan glycoside, seco-dehydrodiconiferyl alcohol-4-O-ß-D-glucopyranoside, together with eight known compounds, were obtained from the EtOH extract of the root bark of Ailanthus altissima. Their structures were elucidated based on the spectroscopic data. Three neolignan glycosides including 7,9,9'-trihydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan-4-O-ß-D-glucopyranoside, sonchifolignan B and citrusin B exhibited moderate in vitro inhibitory effect on tobacco mosaic virus replication with IC50 values 0.30, 0.35 and 0.26 mmol L⻹, respectively.
Asunto(s)
Ailanthus/química , Glicósidos/química , Lignanos/química , Raíces de Plantas/química , Glicósidos/farmacología , Lignanos/farmacología , Virus del Mosaico/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
Two new compounds named fischeacid and fischexanthone, together with eight known compounds, were obtained from the culture of a marine-derived fungus Neosartorya fischeri strain 1008F1. The structures of the new compounds were elucidated based on the spectroscopic data. Bioassays indicated that AGI-B4 and 3,4-dihydroxybenzoic acid showed potent inhibitory effect on the replication of tobacco mosaic virus, and AGI-B4 also possessed an inhibition of the cell proliferation of human gastric cancer cell line SGC-7901 and hepatic cancer cells BEL-7404.
Asunto(s)
Neosartorya/química , Antineoplásicos/química , Antineoplásicos/farmacología , Antivirales/química , Antivirales/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Estructura Molecular , Virus del Mosaico del Tabaco/efectos de los fármacosRESUMEN
In this study, two novel flavan derivatives, namely, rhusjavanins A and B, along with two known flavans 2,3-trans-3,4-trans-3,4,7,4'-tetrahydroxyflavan and 2,3-trans-3,4-cis-3,4,7,4'-tetrahydroxyflavan, have been isolated from the roots of Rhus javanica. The structures were elucidated on the basis of spectroscopic data.
Asunto(s)
Raíces de Plantas/química , Rhus/química , Espectroscopía de Resonancia Magnética , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría Infrarroja , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
A new phenolic glycoside, 4-O-ß-D-apifuranosyl-(1â2)-ß-D-glucopyranosyl-2-hydroxy-6-methoxyacetophenone (2) and 11 known compounds were isolated from the MeOH extract of the plant Celosia argentea. The structures of the compounds were elucidated on the basis of spectroscopic analysis and chemical methods. Among the isolated compounds, stigmasterol (10) showed moderate inhibitory activities against SGC-7901 and BEL-7404 cells.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Celosia/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Fenoles/aislamiento & purificación , Fenoles/farmacología , Antineoplásicos Fitogénicos/química , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Glicósidos/química , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Fenoles/química , Estereoisomerismo , Estigmasterol/farmacologíaRESUMEN
Three new water-soluble compounds, pungens A-C, along with four known compounds including two phenol glycosides, one secoiso-flavanol and one phenol ether, have been isolated from the bark of Elaeagnus pungens. Among them, pungen C (7) (200 microg/ml) was tested in SGC-7901 and BEL-7404 tumor cell lines, and showed moderate cytotoxic activity. The structures of the new compounds were elucidated on the basis of spectroscopic data and chemical evidence.
Asunto(s)
Anisoles/aislamiento & purificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Medicamentos Herbarios Chinos/química , Elaeagnaceae/química , Ácido Gálico/análogos & derivados , Saponinas/aislamiento & purificación , Anisoles/química , Antineoplásicos Fitogénicos/química , Ensayos de Selección de Medicamentos Antitumorales , Flavonoides/química , Flavonoides/aislamiento & purificación , Ácido Gálico/química , Ácido Gálico/aislamiento & purificación , Ácido Gálico/farmacología , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Fenoles/química , Fenoles/aislamiento & purificación , Corteza de la Planta/química , Quinazolinonas/química , Quinazolinonas/aislamiento & purificación , Saponinas/químicaRESUMEN
OBJECTIVE: To identify two marine fungi and evaluate the inhibitory effects of their crude extracts on Tobacco mosaic virus and two tumor cell lines. METHODS: Crude extracts was obtained by extracting with MeOH and evaporated in vacuo. The extracts was water-soluble fraction which was dissolved in water, and the other fraction was water insoluble. The fungi were identified by morphology and Internal Transcribed Spcer (ITS) rDNA molecular methods. The inhibitory effect on Tobacco mosaic virus was evaluated by indirect enzyme linked immunosorbent assay, and the anti-tumor activity was tested by methyl thiazolyl tetrazolium method. RESULTS: The fungi were identified as Penicillium oxalicum and Neosartorya fischeri. There crude extracts inhibited Tobacco Mosaic Virus and two tumor cell lines. The active fraction named 0312F1 inhibited Tobacco Mosaic Virus and tumor cell lines and was water-soluble. The fraction named 1008F1 inhibited Tobacco Mosaic Virus and was insoluble in water, whereas the fraction inhibited tumor cell lines was water-soluble. CONCLUSION: The active fraction named 0312F1 inhibited Tobacco Mosaic Virus was different from that named 1008F1 inhibited Tobacco Mosaic Virus. The active fraction named 0312F1 inhibited tumor cell lines was the same as that named 1008F1. Furthermore, the inhibitory activity of water-soluble fraction named 0312F1 against BEL-7404 cell line was much higher than that against SGC-7901 cell lines, whereas the inhibitory activity of active fraction named 1008F1 against SGC-7901 cell line was much higher.
Asunto(s)
Antineoplásicos/farmacología , Antivirales/farmacología , Neosartorya/química , Neosartorya/aislamiento & purificación , Penicillium/química , Penicillium/aislamiento & purificación , Agua de Mar/microbiología , Línea Celular Tumoral , Hongos/clasificación , Hongos/genética , Humanos , Datos de Secuencia Molecular , Neosartorya/clasificación , Neosartorya/genética , Penicillium/clasificación , Penicillium/genética , Filogenia , Virus del Mosaico del Tabaco/efectos de los fármacosRESUMEN
BACKGROUND: Marine fungi are of great importance as potential sources of agricultural pesticide leads. To continue work on new and biologically active metabolites from marine fungi, culture extracts of selected isolates were screened for inhibitory activity against tobacco mosaic virus (TMV), a typical member of the tobamovirus group of plant viruses. RESULTS: A new difuranxanthone, asperxanthone (1), and a new biphenyl, asperbiphenyl (2), as well as seven known unsaturated fatty acid glycerol esters, were isolated from a selected marine fungus, identified as Aspergillus sp. (MF-93), collected in the Quan-Zhou Gulf. Two-dimensional NMR methods and FAB-MS established the structures of the new compounds. Among the compounds, 1 and 2 showed moderate activity (inhibitory rates 62.9 and 35.5% respectively) in inhibiting multiplication of TMV, higher than that of the other seven known lipids but much lower than that of the extract at the identical concentration of 0.2 mg mL(-1). CONCLUSION: Two new compounds, asperxanthone and asperbiphenyl, were identified as active components from Aspergillus sp. (MF-93).