RESUMEN
To explore active natural products against tobacco powdery mildew caused by Golovinomyces cichoracearum, an extract from the fermentation of endophytic Aspergillus fumigatus 0338 was investigated. The mechanisms of action for active compounds were also studied in detail. As a result, 14 indole alkaloid derivatives were isolated, with seven being newly discovered (1-7) and the remaining seven previously described (8-14). Notably, compounds 1-3 are rare linearly fused 6/6/5 tricyclic prenylated indole alkaloids, with asperversiamide J being the only known natural product of this kind. The isopentenyl substitutions at the 5-position in compounds 4 and 5 are also rare, with only compounds 1-(5-prenyl-1H-indol-3-yl)-propan-2-one (8) and 1-(6-methoxy-5-prenyl-1H-indol3-yl)-propan-2-one currently available. In addition, compounds 6 and 7 are new framework indole alkaloid derivatives bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. The purified compounds were evaluated for their activity against G. cichoracearum, and the results revealed that compounds 7 and 9 demonstrated obvious anti-G. cichoracearum activities with an inhibition rate of 82.6% and 85.2%, respectively, at a concentration of 250 µg/mL, these rates were better than that of the positive control agent, carbendazim (78.6%). The protective and curative effects of compounds 7 and 9 were also better than that of positive control, at the same concentration. Moreover, the mechanistic study showed that treatment with compound 9 significantly increased the structural tightness of tobacco leaves and directly affect the conidiospores of G. cichoracearum, thereby enhancing resistance. Compounds 7 and 9 could also induce systemic acquired resistance (SAR), directly regulating the expression of defense enzymes, defense genes, and plant semaphorins, which may further contribute to increased plant resistance. Based on the activity experiments and molecular dockings, the indole core structure may be the foundation of these compounds' anti-G. cichoracearum activity. Among them, the indole derivative parent structures of compounds 6, 7, and 9 exhibit strong effects. Moreover, the methoxy substitution in compound 7 can enhance their activity. By isolating and structurally identifying the above indole alkaloids, new candidates for anti-powdery mildew chemical screening were discovered, which could enhance the utilization of N. tabacum-derived fungi in pesticide development.
Asunto(s)
Alcaloides , Aspergillus fumigatus , Neopreno , Nicotiana , Alcaloides Indólicos/farmacología , Alcaloides Indólicos/química , Alcaloides/farmacologíaRESUMEN
Alkyl salicylaldehyde derivatives are polyketide natural products, which are widely distributed in fungi and exhibit great structural diversity. Their biosynthetic mechanisms have recently been intensively studied; however, how the polyketide synthases (PKSs) involved in the fungal alkyl salicylaldehyde biosyntheses release their products remained elusive. In this study, we discovered an orphan biosynthetic gene cluster of salicylaldehyde derivatives in the fungus Stachybotrys sp. g12. Intriguingly, the highly reducing PKS StrA, encoded by the gene cluster, performs a reductive polyketide chain release, although it lacks a C-terminal reductase domain, which is typically required for such a reductive release. Our study revealed that the chain release is achieved by the ketoreductase (KR) domain of StrA, which also conducts cannonical ß-keto reductions during polyketide chain elongation. Furthermore, we found that the cupin domain-containing protein StrC plays a critical role in the aromatization reaction. Collectively, we have provided an unprecedented example of a KR domain-catalyzed polyketide chain release and a clearer image of how the salicylaldehyde scaffold is generated in fungi.
Asunto(s)
Policétidos , Sintasas Poliquetidas/metabolismo , Aldehídos , CatálisisRESUMEN
In this study, seven novel anthraquinones (1-7) and four described anthraquinones (8-11) were purified from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220. It is worth noting that only analogs of 4 and 5 have been reported as natural products to date, while the nuclei of compounds 1-3, 6 and 7 were isolated for the first time in nature. Among them, compounds 1-3 bear an unusual anthra[2,3-b]furan-9,10-dione nucleus, 4 and 5 possess a rare 3-methyl-1H-pyrrol-2-yl substituent, and 6 and 7 are new framework anthraquinones bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. Interestingly, the in vivo assays indicated that 1, 4 and 5 had inactivation effects against tobacco mosaic virus (TMV) with inhibition rates of 41.6%, 55.4% and 38.6%, respectively, at a concentration of 50 µg/mL, which were better than that of the positive control agent, ningnanmycin (33.8%). Compounds 1, 4 and 5 also had protective effects with inhibition rates of 48.7%, 60.2% and 43.5% at the same concentration, while 4 had a better curative effect than ningnanmycin at a concentration of 100 µg/mL. In addition, mechanistic studies also revealed that a potent direct effect on TMV, the induction of SAR in tobacco plants, and the effective regulation of defense enzymes, defense genes, and defense hormones may be the reasons for the significant effects of 4 against TMV. At the same time, downregulation of the expression of total NtHsp70 protein by inhibiting the related Hsp70 genes may also be involved in tobacco resistance to TMV. To evaluate whether compounds have broader antiviral activities, the antirotavirus activities of new isolates were also evaluated and found to be highly effective with a therapeutic index (TI) value ranging from 11.6 to 17.7. This study suggests that the above anthraquinone compounds, particularly 4, have broad spectrum antiviral activities. The successful isolation and structure identification of the above anthraquinones provide new materials for the screening of anti-TMV agents and contribute to the improved utilization of N. tabacum-derived fungi.
Asunto(s)
Aspergillus oryzae , Virus del Mosaico del Tabaco , Nicotiana , Antraquinonas/farmacología , Bioensayo , Antivirales/farmacologíaRESUMEN
Two new sesquiterpene aryl esters, armimelleolides A and B (1 and 2), and four known ones, were isolated from the EtOAc extract of Armillaria gallica 012 m by column chromatography on silica gel, reversed-phase C18 silica gel and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic methods, including extensive 1 D NMR, 2 D NMR and MS. All these compounds showed potential antitumor activities against at least one of the human cancer cell lines (A549, HCT-116, M231 and W256), with IC50 ranging from 2.57 to 19.94 µM.
Asunto(s)
Armillaria , Sesquiterpenos , Ésteres , Estructura Molecular , Sesquiterpenos/farmacologíaRESUMEN
Gregatin A (1) is a fungal polyketide featuring an alkylated furanone core, but the biosynthetic mechanism to furnish the intriguing molecular skeleton has yet to be elucidated. Herein, we have identified the biosynthetic gene cluster of gregatin A (1) in Penicillium sp. sh18 and investigated the mechanism that produces the intriguing structure of 1 by in vivo and in vitro reconstitution of its biosynthesis. Our study established the biosynthetic route leading to 1 and illuminated that 1 is generated by the fusion of two different polyketide chains, which are, amazingly, synthesized by a single polyketide synthase GrgA with the aid of a trans-acting enoylreductase GrgB. Chain fusion, as well as chain hydrolysis, is catalyzed by an α/ß hydrolase, GrgF, hybridizing the C11 and C4 carbon chains by Claisen condensation. Finally, structural analysis and mutational experiments using GrgF provided insight into how the enzyme facilitates the unusual chain-fusing reaction. In unraveling a new biosynthetic strategy involving a bifunctional PKS and a polyketide fusing enzyme, our study expands our knowledge concerning fungal polyketide biosynthesis.
Asunto(s)
Policétidos/metabolismo , Estructura Molecular , Sintasas Poliquetidas/química , Sintasas Poliquetidas/metabolismo , Policétidos/química , EstereoisomerismoRESUMEN
A new isoquinoline alkaloid(1) has been isolated from the whole plant of Thalictrum glandulosissimum by using various chromatographic techniques, including silica gel, sephadex, MCI-gel resin, and RP-HPLC, and its structure was determined as 1-(6-hydroxy-7-methylisoquinolin-1-yl) ethantone by physicochemical properties and spectroscopic data. This compound was evaluated for anti-tobacco mosaic virus(TMV) activity. The results showed that it had prominent anti-TMV activity with inhibition rates of 28.4%. This rate was closed to that of positive control.
Asunto(s)
Alcaloides , Antivirales , Thalictrum , Virus del Mosaico del Tabaco , IsoquinolinasRESUMEN
A new isobenzoisofuran(1) has been isolated from the whole plant of Cassia pumila using various chromatographic techniques, including silica gel, Sephadex, MCI-gel resin, and RP-HPLC, and its structure was determined as 9-(2-hydroxyethyl)-2,2-dimethyl-2H-furo[3,4-g]chromen-6(8H)-one. This compound was also evaluated for its antibacterial activity. The results showed that it had prominent antibacterial activity with MIC_(90) value of(45.2±4.2) µg·mL~(-1) for methicillin resistant Staphylococcus aureus(MRSA) strain. This value was closed to that of levofloxacin [with MIC_(90) value(48.5±4.3) µg·mL~(-1)].
Asunto(s)
Antibacterianos/farmacología , Benzofuranos/farmacología , Cassia/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Antibacterianos/aislamiento & purificación , Benzofuranos/aislamiento & purificación , Levofloxacino , Pruebas de Sensibilidad Microbiana , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Plantas Medicinales/químicaRESUMEN
Three new diphenyl ethers (1-3), together with four known isopentylated diphenyl ethers derivatives (4-7), were isolated from the fermentation products of an endophytic fungus Phomopsis fukushii. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1-3 were evaluated for their anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity. The results revealed that compounds 1 and 2 showed strong inhibitions with inhibition zone diameters (IZD) of 20.2 ± 2.5 mm and 17.9 ± 2.2 mm, respectively. Compound 3 also showed good inhibition with IZD 15.2 ± 1.8 mm. The IZD data of compound 1 is close to that of positive control with IZD 21.9 ± 2.1 mm.
Asunto(s)
Ascomicetos/metabolismo , Endófitos/metabolismo , Fermentación , Éteres Fenílicos/aislamiento & purificación , Éteres Fenílicos/química , Éteres Fenílicos/farmacologíaRESUMEN
A new flavone( 1) has been isolated from the whole plant of Cassia nomame by using various chromatographic techniques,including silica gel,Sephadex,MCI-gel resin,and RP-HPLC,and its structure was determined as 8,4'-dimethoxy-7-( 2-oxopropyl)-flavone based on spectroscopic data. The biological activity test showed that this compound displayed potent cytotoxicity against NB4,SH-SY5 Y,PC3,A549 and MCF-7 cell lines with IC50 values 2. 2,1. 8,3. 4,4. 5 and 1. 6 µmol·L-1,respectively.
Asunto(s)
Cassia , Flavonas , Senna , Cromatografía Líquida de Alta Presión , Humanos , Células MCF-7RESUMEN
A new naphthaldehyde derivative has been isolated from Comastoma pulmonarium by using various chromatographic techniques, including silica gel, Sephadex LH-20, MCI-gel resin and RP-HPLC. This compounds was determined as 5-methoxy-2-methyl-7-(2-oxopropyl)naphthalene-1-carbaldehyde(1) by NMR, MS, IR and UV spectra. This compound was also evaluated for its anti-tobacco mosaic virus (anti-TMV) activity. The result showed that it showed high anti-TMV activity with inhibition rate of 32.8%. The inhibition rate is close to that of positive control (ningnanmycin).
Asunto(s)
Aldehídos/farmacología , Antivirales/farmacología , Gentianaceae/química , Naftalenos/farmacología , Virus del Mosaico del Tabaco/efectos de los fármacos , Aldehídos/aislamiento & purificación , Antivirales/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Naftalenos/aislamiento & purificación , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , NicotianaRESUMEN
A new isobenzofuranone derivative has been isolated from Phlomis betonicoides by using various chromatographic techniques, including silica gel, Sephadex LH-20, MCI-gel resin and RP-HPLC. This compound was determined as 5-(3-hydroxypropyl)-2,2-dimethyl-2H-furo[3,4-h]chromen-7(9H)-one (1) by NMR, MS, IR and UV spectroscopic data. Compound 1 showed potent antibacterial activity with an MIC90 value of (58.4 ± 4.2) mg·L⻹ for methicillin resistant Staphylococcus aureus (MRSA) strain [levofloxacin as a control with MIC90 value of (52.8±4.6) mg·L⻹].
Asunto(s)
Antibacterianos/farmacología , Benzofuranos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Phlomis/química , Antibacterianos/aislamiento & purificación , Benzofuranos/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacologíaRESUMEN
A new isoflavone derivative was isolated from Rosa damascena by using various chromatographic techniques including silica gel, Sephadex LH-20, and preparative RP-HPLC separation. Its structure was identified as 4'-hydroxy-7-(3-hydroxypropanoyl)-6-methoxy-isoflavone using combined examinations of their UV, IR, MS, and NMR spectroscopic data. Biological activity test showed that this compound showed prominent antibacterial activity with MIC90 value of (46±4) mg·L⻹ for methicillin resistant Staphylococcus aureus(MRSA) strain. This value is close to that of levofloxacin [with MIC90 value (53±5) mg·L⻹].
Asunto(s)
Antibacterianos/farmacología , Isoflavonas/farmacología , Rosa/química , Antibacterianos/aislamiento & purificación , Isoflavonas/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacologíaRESUMEN
Three new C-alkylated flavonoids, 4'-hydroxy-8-isobutyryl-7-methoxy-6-methyl-flavone (1), 4',7-dimethoxy-8-isobutyryl-6-methyl-flavone (2), and 4',7-dimethoxy-8-isobutyryl-flavone (3), together with three know ones luteolin (4), kaemferol (5), and quercetin (6), were isolated from Desmodium oblongum. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. Compound 1 showed cytotoxicity against NB4, SHSY5Y, and MCF7 cell lines with IC50 values of 8.5, 6.5, and 7.8 µM; compound 2 showed cytotoxicity against SHSY5Y and PC3 cell lines with IC50 values of 5.0 and 6.8 µM; compound 3 displayed cytotoxicity against SHSY5Y and MCF7 cell lines with IC50 values of 6.4 and 9.4 µM, respectively.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Fabaceae/química , Flavonas/aislamiento & purificación , Alquilantes , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Flavonas/química , Flavonas/farmacología , Humanos , Concentración 50 Inhibidora , Células MCF-7 , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Three previously unreported anthraquinones, fistulaquinones A-C (1-3), together with three known ones (4-6) were isolated from the twigs of Cassia fistula. Their structures were determined by means of extensive NMR and MS spectroscopic analyses. All the isolated compounds were tested for their anti-tobacco mosaic virus (anti-TMV) activity, and compound 3 showed significant activity with inhibition rate of 34.5% at 20 µM concentration, even more potent than positive control. Additionally, compounds 1-6 exhibited moderate cytotoxicity with IC50 values ranging from 2.8 to 9.4 µM for some tested human tumor cell lines.
Asunto(s)
Antraquinonas/aislamiento & purificación , Antraquinonas/farmacología , Antivirales/aislamiento & purificación , Antivirales/farmacología , Cassia/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Virus del Mosaico del Tabaco/efectos de los fármacos , Antraquinonas/química , Antivirales/química , Citidina/análogos & derivados , Citidina/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Paclitaxel/farmacología , Hojas de la Planta/química , Tallos de la Planta/químicaRESUMEN
We have carried out the chemical investigation on the roots of Alangium chinense. The chemical constituents from the roots of A.chinense were isolated and purified by various chromatographic techniques, such as silica gel, MCI-Gel resin, Sephadex LH-20 and high performance liquid chromatography. As a result, three alkaloids (1-3) were isolated from 90% EtOH extracts of the roots of this plant. Their structures were elucidated by physical-chemical properties and spectral data. Among them, compound 1 is a new compound, determined as 8-hydroxy-3-hydroxymethyl-6,9-dimethyl-7H-benzo[de]isoquinolin-7-one. Cytotoxicity of the compounds was evaluated by the MTT method. Compound 1 displayed cytotoxicity against NB4, A-549, SHSY5Y, PC-3 and MCF-7 cell lines with IC50 values of 4.2, 3.5, 5.7, 2.8 and 3.9 µmolâ¢L⻹, respectively.
Asunto(s)
Alangiaceae/química , Alcaloides/aislamiento & purificación , Raíces de Plantas/química , Línea Celular Tumoral , Humanos , Fitoquímicos/aislamiento & purificaciónRESUMEN
A new naphthalene derivative has been isolated from Aloe vera by using various chromatographic techniques, including silica gel, sephadex, MCI-gel resin, and RP-HPLC. The new compound was determined as 3-hydroxy-1-(1,7-dihydroxy-3,6-dimethoxynaphthalen-2-yl)propan-1-one (1). In the biological activity assay, compound 1 disglayed prominent antibacterial activity with a MIC90 value of (48±4) mgâ¢L⻹ for methicillin resistant Staphylococcus aureus (MRSA) strain which was stronger than that of the positive control levofloxacin with a MIC90 value (58±5) mgâ¢L⻹.
Asunto(s)
Aloe/química , Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Naftalenos/farmacología , Antibacterianos/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Naftalenos/aislamiento & purificación , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacologíaRESUMEN
Five new diterpenoids (1-5) were isolated from the roots of Aralia melanocarpa, together with four known compounds, 7ß-hydroxy-ent-pimara-8(14),15-diene-19-oic acid (6), 18-norpimara-8(14),15-dien-4-ol (7), ent-16ßH,17-isovalerate-kauran-19-oic acid (8), and ent-16α,17-dihydroxykauran-19-oic acid (9). Based on the MS, IR, and NMR spectral analysis, the structures of the five new diterpenoids (1-5) were elucidated. The cytotoxic activities of compounds 1-9 were assayed, and compounds 1 and 2 showed cytotoxicity in four cancer cell lines with IC50s from 4.2 to 8.2 µM.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Aralia/química , Diterpenos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Línea Celular , Diterpenos/química , Diterpenos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Raíces de Plantas/químicaRESUMEN
Oryzaeins A-D (1-4), four new isocoumarin derivatives, along with five known ones (5-9) were isolated from solid cultures of an endophytic fungus Aspergillus oryzae. Their structures were elucidated by detailed spectroscopic analysis and by comparison with reported data of related derivatives. Among them, compounds 1 and 2 represent the first examples of isocoumarins possessing an unusual 2-oxopropyl group and a rare 3-hydroxypropyl group. Compounds 1 and 2 displayed moderate anti-tobacco mosaic virus activities with inhibition rates of 28.4% and 30.6%, respectively, at the concentration of 20 µM. The new compounds showed moderate inhibitory activities against several human tumor cell lines with IC50 values in the range of 2.8-8.8 µM. Supporting information available online at http://www.thieme-connect.de/products.
Asunto(s)
Antineoplásicos/farmacología , Antivirales/farmacología , Aspergillus oryzae/química , Isocumarinas/farmacología , Virus del Mosaico del Tabaco/efectos de los fármacos , Antibacterianos/farmacología , Antineoplásicos/aislamiento & purificación , Antivirales/aislamiento & purificación , Línea Celular Tumoral , China , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura MolecularRESUMEN
Phytochemical investigations on the ethanol extract of the twigs of Garcinia tetralata resulted in the isolation of three new biphenyls, tetralatabiphenyls A-C (1-3), along with three known biphenyl derivatives (4-6). Structural elucidations of 1-3 were performed by spectroscopic methods such as 1D and 2D NMR spectra, in addition to high-resolution mass spectra. Compounds 1-6 were also evaluated for their anti-tobacco mosaic virus (anti-TMV) activity. The results showed that compound 3 showed high anti-TMV activity with inhibition rate of 31.1%. Compounds 1, 2, and 4-6 also showed modest anti-TMV activities with inhibition rates in the range of 18.9-24.5%, respectively.
Asunto(s)
Antivirales/aislamiento & purificación , Antivirales/farmacología , Compuestos de Bifenilo/aislamiento & purificación , Compuestos de Bifenilo/farmacología , Garcinia/química , Virus del Mosaico del Tabaco/efectos de los fármacos , Antivirales/química , Compuestos de Bifenilo/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Tallos de la Planta/químicaRESUMEN
A new furan-2-carboxylic acid, 5-[3-(hydroxymethyl)-4,5-dimethoxyphenyl]-3-methylfuran-2-carboxylic acid(1),has been isolated from the bark of Cassia alata by using various chromatographic techniques. It displayed cytotoxicity against NB4, A549, SHSY5Y, PC3 and MCF7 cell lines with IC50 values of 2.5, 1.2, 2.2, 3.6 and 1.9 µmolâ¢L⻹, respectively.