RESUMEN
Spectasterols F-O (1-10), ten interesting ergosterols with an aromatized B ring, were obtained from Aspergillus spectabilis. Their structures and absolute configurations were determined using a combination of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), nuclear magnetic resonance (NMR) spectroscopy, single-crystal X-ray diffraction analyses, and electronic circular dichroism (ECD) calculations. Structurally, these aromatic ergosterols feature versatile side chains. Notably, compound aromatic ergosterols featured versatile side chains, and compound 4 is an unusual C23 ergosterol characterized by a shorter side chain due to oxidative cleavage between C-23 and C-24. All compounds were evaluated for their neuroprotective activities, with compound 8 showing a dose-dependent ability to reduce apoptosis and protect mitochondrial function in glutamate-induced SH-SY5Y cells.
Asunto(s)
Aspergillus , Ergosterol , Fármacos Neuroprotectores , Aspergillus/química , Ergosterol/química , Ergosterol/farmacología , Ergosterol/análogos & derivados , Humanos , Estructura Molecular , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Espectroscopía de Resonancia MagnéticaRESUMEN
Ten ergostane-type steroids, including seven undescribed ones named spectasteroids A-G, were obtained from Aspergillus spectabilis. Their structures and absolute configurations were determined based on HRESIMS, NMR, ECD calculations, and single-crystal X-ray diffraction analyses. Structurally, spectasteroid A was a unique example of aromatic ergostane-type steroid that featured a rare peroxide ring moiety; spectasteroid B contained a rare oxetane ring system formed between C-9 and C-14; and spectasteroid C was an unusual 3,4-seco-ergostane steroid with an extra lactone ring between C-3 and C-9. Spectasteroids F and G specifically showed inhibitory effects against concanavalin A-induced T lymphocyte proliferation and lipopolysaccharide-induced B lymphocyte proliferation, with IC50 values ranging from 2.33 to 4.22 µM. Spectasteroid F also showed excellent antimultidrug resistance activity, which remarkable enhanced the inhibitory activity of PTX on the colony formation of SW620/Ad300 cells.
Asunto(s)
Aspergillus , Inmunosupresores , Peróxidos , Aspergillus/química , Inmunosupresores/farmacología , Inmunosupresores/química , Inmunosupresores/aislamiento & purificación , Peróxidos/química , Peróxidos/farmacología , Peróxidos/aislamiento & purificación , Estructura Molecular , Humanos , Lactonas/química , Lactonas/farmacología , Lactonas/aislamiento & purificación , Ergosterol/química , Ergosterol/farmacología , Ergosterol/aislamiento & purificación , Ergosterol/análogos & derivados , Proliferación Celular/efectos de los fármacos , Éteres Cíclicos/química , Éteres Cíclicos/farmacología , Éteres Cíclicos/aislamiento & purificación , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Ratones , Linfocitos T/efectos de los fármacosRESUMEN
Seven undescribed compounds (1-7) along with six known compounds (8-13) were isolated from Eurotiaceae Aspergillus quadrilineatus. Their structures and absolute configurations were elucidated by NMR, HRESIMS, and ECD calculations. Quadrilisteroids A (1) and B (2) possessed an unprecedented 6/5/6/6/6/5 hexacyclic ring system in conjugation with a highly fused benzene ring, while quadrilisteroid C (3) featured a surprising 6/6/6/5/5-fused carbocyclic skeleton. Quadrilisteroid C (3) exhibited potent inhibitory activity against LPS-induced proliferation of B lymphocyte cells with an IC50 value of 1.03 µM. Compound 4, demonstrated inhibitory activity against Con A-induced proliferation of T lymphocyte cells with IC50 values of 6.42 µM.
Asunto(s)
Aspergillus , Hongos , Aspergillus/química , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
Four previously undescribed and highly oxygenated α-pyrone-containing mycotoxins designated citreoviridins (EâH), and an unreported eremophilane-type sesquiterpenoid namely aureoterrolide N, were isolated from the culture broth of Aspergillus aureoterreus. Those isolates were inferred from extensive spectroscopic methods and theoretical computation, where their absolute configurations were unambiguously determined by coupling constants following an empirical rule for the acyclic vicinal diol, theoretical ECD calculation, and NMR computation using the GIAO method and DP4+ analysis. Among them, citreoviridins EâH are four stereoisomers of a citreoviridin derivative, featuring a methylated α-pyrone, an oxidized polyene linker, and a tetrahydrofuran ring. Cytotoxicity assay of all isolates demonstrated that aureoterrolide N exhibited weak inhibitory effect against human cancer cell line HL-60 with an inhibition rate of 55.2% at 40.0 µM.
Asunto(s)
Aspergillus , Micotoxinas , Sesquiterpenos , Humanos , Pironas/farmacología , Pironas/química , Micotoxinas/farmacología , Estructura Molecular , Sesquiterpenos Policíclicos , Sesquiterpenos/farmacología , Espectroscopía de Resonancia MagnéticaRESUMEN
Three new furano-lactones, asperilactones A-C (1-3), and two known compounds silvaticol (4) and violaceic acid (5) were isolated from an ethanol extract of Aspergillus nidulans, a fungus isolated from the Annelida Whitmania pigra Whitman (Haemopidae). Their structures were elucidated by a combination of spectroscopy, ECD calculations, comparing optical rotation values, and single-crystal X-ray diffraction analyses. Asperilactone A (1) represented the first example of furano-lactone with an unusual 2-thia-6-oxabicyclo[3.3.0]octane ring system. Asperilactones A and B showed weak toxicity against the HL-60 and RKO.
Asunto(s)
Aspergillus nidulans , Lactonas/química , Estructura Molecular , Cristalografía por Rayos X , Análisis EspectralRESUMEN
Quadristerols A-G, seven undescribed ergosterols, were obtained from Aspergillus quadrilineata. Their structures and absolute configurations were determined based on HRESIMS, NMR, quantum-chemical calculations, and single-crystal X-ray diffraction analyses. Quadristerols A-G featured ergosterol skeletons with different attachments; quadristerols A-C were three diastereoisomers possessing a 2-hydroxy-propionyloxy group at C-6, and quadristerols D-G were two pairs of epimers with a 2,3-butanediol group at C-6. All of these compounds were evaluated for their immunosuppressive activities in vitro. Quadristerols B and C showed excellent inhibitory effects against concanavalin A-induced T lymphocyte proliferation with IC50 values of 7.43 and 3.95 µM, respectively, and quadristerols D and E strongly inhibited lipopolysaccharide-induced B lymphocyte proliferation with IC50 values of 10.96 and 7.47 µM, respectively.
Asunto(s)
Aspergillus , Ergosterol , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética , Ergosterol/farmacología , Aspergillus/química , Estructura MolecularRESUMEN
Twelve new fungal polyketides, koningiopisins I-P (1-8) and trichoketides C-F (9-12), together with six known congeners (13-18), were isolated from Trichoderma koningiopsis, a rhizosphere fungus obtained from the medicinal plant Polygonum paleaceum. Their structures and absolute configurations were established by spectroscopic analysis, single-crystal X-ray diffraction, the modified Mosher's method, chemical derivatization, the octant rule, and 13C NMR and ECD calculations. Compounds 1-5 are tricyclic polyketides possessing an octahydrochromene framework with a 6,8-dioxabicyclo[3.2.1]octane core. Compounds 7 and 8 contain a unique ketone carbonyl group at C-7 and differ from other members of this group of compounds with the ketone carbonyl group at C-1. Compounds 1, 2, and 13 showed inhibitory activity on LPS-induced BV-2 cells on NO production with IC50 values of 14 ± 1, 3.0 ± 0.5, and 8.9 ± 2.7 µM, respectively.
Asunto(s)
Plantas Medicinales , Polygonum , Policétidos , Policétidos/química , Rizosfera , Estructura Molecular , Espectroscopía de Resonancia Magnética , HongosRESUMEN
Spectasterols A-E (1-5), aromatic ergosterols with unique ring systems, were isolated from Aspergillus spectabilis. Compounds 1 and 2 possess a 6/6/6/5/5 ring system with an additional cyclopentene, while 3 and 4 have an uncommon 6/6/6/6 ring system generated by the D-ring expansion via 1,2-alkyl shifts. Compound 3 exhibited cytotoxic activity (IC50 6.9 µM) and induced cell cycle arrest and apoptosis in HL60 cells. Compound 3 was anti-inflammatory; it decreased COX-2 levels at the transcription and protein levels and inhibited the nuclear translocation of NF-κB p65.
Asunto(s)
Aspergillus , FN-kappa B , Humanos , FN-kappa B/metabolismo , Aspergillus/metabolismo , Antiinflamatorios/farmacología , Apoptosis , Ergosterol/farmacologíaRESUMEN
Three new acetylenic aromatic compounds, sterehirsutynes A-C (1-3), along with three known congeners, frustulosinol (4), vibrayne (5), and sterehirsutinol (6), were isolated from the culture broth of Stereum hirsutum. Their structures were determined by detailed analyses of NMR and high-resolution mass. Chiral column analysis showed that compounds 2 and 3 were racemic mixtures. These new compounds were evaluated for porcine pancreatic lipase (PPL) inhibitory activities, and compounds 1 and (±) 3 showed moderate inhibitory activity against PPL, with IC50 values of 23.2 ± 1.04 and 21.8 ± 2.15 µM, respectively.
Asunto(s)
Acetileno , Animales , Porcinos , Páncreas/enzimología , Lipasa/metabolismo , Acetileno/química , Acetileno/farmacologíaRESUMEN
Four emestrin hybrid polymers, asperemestrins A-D (1-4, respectively), were isolated from the fungus Aspergillus nidulans. Asperemestrins A-C are the first examples of emestrin-sterigmatocystin heterodimers bearing a 7/5/6/6/5/5/6/6/6 nonacyclic system with a 2,5-diazabicyclo[2.2.2]octane-3,6-dione core, while asperemestrin D features an unprecedented 2,15-dithia-17,19-diazabicyclo[14.2.2]icosa-4,8-diene-12,18,20-trione core skeleton. Their structures were determined by extensive spectroscopic data, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Asperemestrin B showed moderate cytotoxicity against cancer cell lines, including SU-DHL-2, HEPG2, and HL-60.
Asunto(s)
Aspergillus nidulans , Aspergillus nidulans/metabolismo , Dicroismo Circular , Humanos , Estructura Molecular , Octanos , Piperazinas , Polímeros , Esterigmatocistina/metabolismoRESUMEN
A document investigation on the fungus Trichoderma virens led to the isolation of thirteen undescribed carotane sesquiterpenes and homologous. All structures were elucidated on the basis of NMR and HRESIMS data, and their absolute configurations were assigned by ECD calculation. Especially, virenscarotins A and B were first ramifications forged by aldol condensation of 4-hydroxy-3-isopentenyl-benzaldehyde with two hydroxyl groups in ring A of traditional carotane sesquiterpenes. Ring rearrangement/expansion and oxidative cleavage of normal carotane sesquiterpenes lead to the six-membered ring A of compound virenscarotin C and the ring A cleavage of compound virenscarotin D. All compounds were evaluated for cytotoxic, anti-inflammatory, and seed germination inhibitory activities.
Asunto(s)
Hypocrea , Sesquiterpenos , Trichoderma , Benzaldehídos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Sesquiterpenos/química , Trichoderma/químicaRESUMEN
Uncovered by genome sequence analyses, twelve undescribed sesquiterpenoids designated aureoterrolides BâM, were isolated from the culture broth of the fungus Aspergillus aureoterreus together with two known analogues. They are unusual eremophilanes with an oxidized C-4, of which aureoterrolide J is an unreported furanoeremophilane comprising a 3/6/6/5/3 pentacyclic architecture with a rare 3,6-spiro ring system. Their structures and absolute configurations were unambiguously assigned by extensive spectroscopic method and theoretical ECD calculation. All isolated compounds were evaluated their cytotoxicity, and aureoterrolides A, B, and I-K showed moderate cytotoxic activity against three human cancer cell lines (HL-60, HepG-2, and SKOV-3) with IC50 values ranging from 4.53 ± 0.05 to 24.71 ± 0.16 µM. Among them, aureoterrolide A exhibited activity such close to the positive control and apoptotic effect on HL-60 cells at a concentration of 5.0 µM.
Asunto(s)
Sesquiterpenos , Aspergillus/química , Humanos , Estructura Molecular , Sesquiterpenos Policíclicos , Sesquiterpenos/químicaRESUMEN
Two undescribed 30-norlanostane triterpenoids, named nidulanoids A and B, one ergostane-type steroid with an unusual double bond between C-17 and C-20 designated (17E,22E,24R)-3ß,5α-dihydroxyergosta-7,17,22-trien-6,16-dione, and one pregnane, (7Z,9Z,17Z)-,2α,3ß-dihydroxypregna-7,9,17 (20)-trien-18-al, along with six known steroids were isolated from the extract of the fungus Aspergillus nidulans. Among them, nidulanosides A and B represents the first example of naturally occurred 30-norlanostane triterpenoids featuring a C9 side-chain moiety at C-17 and a hemiacetal system formed between C-3 and C-19, as an intermediate between lanostane and the regular steriods; the structure of (17E,22E,24R)-3ß,5α-dihydroxyergosta-7,17,22-trien-6,16-dione possesses an untypical Δ17,20 double bond; meanwhile, (7Z,9Z,17Z)-,2α,3ß-dihydroxypregna-7,9,17 (20)-trien-18-al represents the first example of C-21 steroid with an aldehyde group at C-13. Their structures and absolute stereochemistry were elucidated based on spectroscopic data, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. (7Z,9Z,17Z)-,2α,3ß-dihydroxypregna-7,9,17 (20)-trien-18-al showed moderate inhibitory activities against rat brain cancer (PC12) cell lines, with IC50 value of 7.34 µM. This study enriches the diversified structures of triterpenoids and steroids analogues from A. nidulans and indicated (7Z,9Z,17Z)-,2α,3ß-dihydroxypregna-7,9,17(20)-trien-18-al to be a promising lead compound against PC12 cell lines.
Asunto(s)
Aspergillus nidulans , Rhodophyta , Triterpenos , Animales , Dicroismo Circular , Imidazoles , Estructura Molecular , Ratas , Esteroides/química , Sulfonamidas , Tiofenos , Trientina , Triterpenos/farmacologíaRESUMEN
Talaromynoids A-E (1-5), five new fusicoccane diterpenoids, were obtained from the endophytic fungus Talaromyces sp. DC-26, which was isolated from a wild leech. Talaromynoid A (1) represents the first fusicoccane diterpenoid bearing an unexpected 5-7-5 tricyclic ring system, which is possibly derived from normal 5-8-5 ones by ring contraction. Talaromynoid E (5) is characterized by an unusual oxygen bridge between C-1 and C-8 that establishes the eight-membered ring B to be a 9-oxo-bicyclo[3.3.1]nonane. Structures of 1-5 with absolute configurations were determined by extensive NMR spectral analyses, electronic circular dichroism (ECD) calculations, X-ray diffraction analyses, and acid hydrolysis.
Asunto(s)
Diterpenos , Talaromyces , Dicroismo Circular , Cristalografía por Rayos X , Diterpenos/química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Talaromyces/químicaRESUMEN
Two novel cytochalasans, armochaetoglasin J (1) and armochaetoglasin K (2), along with 14 known analogues (3-16) were isolated from Chaetomium globosum. Their structures were elucidated by HRESIMS, NMR spectroscopy, single-crystal X-ray crystallography, and ECD spectra. Armochaetoglasins J and K were found to be inactive against the HepG2, HT-29, K562, HL-60, and A549 cancer cell lines.
Asunto(s)
Chaetomium , Chaetomium/química , Cristalografía por Rayos X , Citocalasinas/química , Células HL-60 , HumanosRESUMEN
Ten sesterterpenoids, including eight undescribed ones named spectanoids A-H and two known analogs, were obtained from Aspergillus spectabilis. Their structures, including absolute configurations, were determined based on HRESIMS, NMR, ECD calculations and single-crystal X-ray diffraction analyses. Spectanoids A-G are tricyclic sesterterpenoids with an unusual 5/12/5 ring system, while spectanoid H possesses a 5/8/6/5 ring system. All of these compounds were evaluated for their cytotoxic activities against three human cancer cells, and spectanoid A, spectanoid C and spectanoid F exhibited moderate cytotoxic activities with IC50 values ranging from 12.1 to 26.1 µM.
Asunto(s)
Aspergillus , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
Eleven undescribed quinolone alkaloids, pesimquinolones I-S (1-4 and 6-12), as well as eleven known congeners (5 and 13-22), were isolated from the solid culture broth of the fungus Penicillium simplicissimum. Their chemical structures with absolute configurations were established by a combination of NMR spectroscopy, single-crystal X-ray crystallography, and modified Mosher's methods. Pesimquinolones I-K (1-3) represent the first examples of natural occurring quinolone alkaloids that possess a 6/6/6/6 tetracyclic ring system. The anti-inflammatory activities of selected compounds on LPS-induced nitric oxide (NO) production in adherent cells were evaluated. Compounds 1 and 2 showed suppressive effects on the production of NO, with IC50 values of 10.13 and 8.10 µM, respectively.
Asunto(s)
Alcaloides/farmacología , Antiinflamatorios/farmacología , Óxido Nítrico/antagonistas & inhibidores , Penicillium/química , Quinolonas/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Ratones , Modelos Moleculares , Estructura Molecular , Óxido Nítrico/biosíntesis , Quinolonas/química , Quinolonas/aislamiento & purificación , Células RAW 264.7 , Relación Estructura-ActividadRESUMEN
Seven undescribed isopimarane diterpene glycosides hypoxylonoids A-G, along with five known analogues were obtained from the fungus Xylaria hypoxylon. The structures and absolute configurations of hypoxylonoids A-G were confirmed by extensive spectroscopic and single-crystal X-ray diffraction analyses. Among these compounds, the γ-lactone moiety formed between C-19 and C-6 of hypoxylonoid A; the 1,2-methyl shift of Me-18 of hypoxylonoids B and E; and the decarboxylation of C-19 of hypoxylonoid E, make them outstanding from the isopimarane family. Single crystal X-ray diffraction analyses of hypoxylonoids A, C, F, and 15-hydroxy-16-α-D-mannopyranosyloxyisopimar-7-en-19-oic acid was performed to determine their absolute structural configuration.
Asunto(s)
Glicósidos , Xylariales , Abietanos , Ascomicetos , Diterpenos , Estructura MolecularRESUMEN
Eight unexpected vibralactone homodimers, bisvibralactones A-H (1-8), and three new vibralactone monomers, hirsutumins A-C (9-11), were isolated from the culture of Stereum hirsutum. Their structures and absolute configurations were determined by detailed analyses of NMR, optical rotations, ECD, and high-resolution mass spectra as well as chemical transformation. Compounds 1-8 are unusual vibralactone dimers formed by the esterification of two vibralactone monomers. The absolute configurations of compounds 1 and 5 were determined by chemical conversions. All of the isolated compounds were evaluated for Porcine Pancreatic Lipase (PPL) inhibitory activities, and compound 10 showed significant inhibitory activity against PPL, with an IC50 value of 8.31 ± 1.04 µM.
Asunto(s)
Basidiomycota/química , Inhibidores Enzimáticos/farmacología , Lactonas/farmacología , Lipasa/antagonistas & inhibidores , Animales , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/metabolismo , Lactonas/química , Lactonas/metabolismo , Lipasa/metabolismo , Estructura Molecular , Páncreas/enzimología , Relación Estructura-Actividad , PorcinosRESUMEN
Eight undescribed quinolone alkaloids, pesimquinolones A-H, as well as six known compounds, were isolated from the solid culture broth of the fungus Penicillium simplicissimum. Their chemical structures were characterized by combined analyses of NMR spectroscopy and single-crystal X-ray crystallography. Pesimquinolones A-G are the first examples of naturally occurring quinolone alkaloids possessing a limonene moiety. Their anti-inflammatory activities on LPS-induced nitric oxide (NO) production in adherent cells were evaluated. Pesimquinolones A, E, G, and H showed promising suppressive effect on the production of NO with IC50 values of 1.94, 1.29, 1.20, and 1.23 µM, respectively.