RESUMEN
A new polyketide, mauritone A (1) with six known polyketides curvulone B (2), curvularin (3), 12-oxocurvularin (4), (10E,15S)-10,11-dehydrocurvularin (5), (11R,15S)-11-hydroxycurvularin (6), and (11S,15S)-11-hydroxycurvularin (7) were isolated from the fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532 derived from Mauritia arabica. Their structures were elucidated by extensive spectral analysis. All compounds (1-7) were evaluated for their anti-inflammatory effects. The inhibitory effects of 4, 5, and 7 on nitric oxide (NO) production were found to be significant, with IC50 values of 5.5 ± 0.26, 2.0 ± 0.31, and 8.3 ± 0.62 µM, respectively, surpassing that of the positive control quercetin (10.6 ± 0.64 µM). Compounds 3 and 6 exhibited moderate inhibition of NO, with IC50 values of 18.6 ± 0.53 and 12.7 ± 0.45 µM, respectively.
RESUMEN
Eight new decahydrofluorene-class alkaloids, microascones A and B (1 and 2), 2,3-epoxyphomapyrrolidone C (3), 14,16-epiascomylactam B (4), 24-hydroxyphomapyrrolidone A (5), and microascones C-E (6-8), along with five known analogs (9-13) were isolated from the marine-derived fungus Microascus sp. SCSIO 41821. Compounds 1 and 2 have an unprecedented complex macrocyclic alkaloid skeleton with a 6/5/6/5/6/5/13 polycyclic system. Their structures and absolute configurations were determined by spectroscopic analysis, quantum chemical calculations of ECD spectra, and 13C NMR chemical shifts. Compounds 10-13 showed selective enzyme inhibitory activity against PTPSig, PTP1B, and CDC25B, and 4, 9, and 10 exhibited strong antibacterial activity against seven tested pathogens. Their structure-bioactivity relationship was discussed, and a plausible biosynthetic pathway for 1-8 was also proposed.
Asunto(s)
Alcaloides , Antibacterianos , Pruebas de Sensibilidad Microbiana , Alcaloides/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Estructura Molecular , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Relación Estructura-Actividad , Biología Marina , Ascomicetos/química , Fluorenos/farmacología , Fluorenos/química , Fluorenos/aislamiento & purificación , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidoresRESUMEN
Two new linear peptides, penicamides A and B (1 and 2), together with four known analogous were isolated from the extracts of the marine-derived fungus Penicillium sp. SCSIO 41512. Their structures were elucidated by analysis of 1D/2D NMR data and HRESI-MS. Their absolute configurations were established by Marfey's methods and quantum chemical calculations.
Asunto(s)
Penicillium , Estructura Molecular , Penicillium/química , Espectroscopía de Resonancia Magnética , Hongos/química , PéptidosRESUMEN
Seven new decahydrofluorene-class alkaloids, pyrrospirones K-Q (1-7), together with six known analogues (8-13) were isolated from the marine-derived fungal strain Penicillium sp. SCSIO 41512. Their structures were determined by extensive spectroscopic analysis, and their absolute configurations were established by single-crystal X-ray diffraction analysis and quantum chemical calculations of electronic circular dichroism spectra. Compounds 1 and 3 possess a novel decahydrofluorene-class alkaloid skeleton with a 6/5/6/8/5/6/13 and a 6/5/6/5/6/13 polycyclic system, respectively. Biologically, 13 displayed significant inhibitory activity against protein tyrosine phosphatases CD45, TCPTP, SHP1, and PTP1B with IC50 values of 8.1-17.8 µM, and 1, 2, 5, 8-10, 12, and 13 showed antibacterial activity against six pathogens. Their structure-activity relationship is also discussed.
Asunto(s)
Alcaloides , Penicillium , Alcaloides/química , Antibacterianos/química , Dicroismo Circular , Hongos/química , Estructura Molecular , Penicillium/químicaRESUMEN
Puniceusines A-N (1-14), 14 new isoquinoline alkaloids, were isolated from the extracts of a deep-sea-derived fungus, Aspergillus puniceus SCSIO z021. Their structures were elucidated by spectroscopic analyses. The absolute configuration of 9 was determined by ECD calculations, and the structures of 6 and 12 were further confirmed by a single-crystal X-ray diffraction analysis. Compounds 3-5 and 8-13 unprecedentedly contained an isoquinolinyl, a polysubstituted benzyl or a pyronyl at position C-7 of isoquinoline nucleus. Compounds 3 and 4 showed selective inhibitory activity against protein tyrosine phosphatase CD45 with IC50 values of 8.4 and 5.6 µM, respectively, 4 also had a moderate cytotoxicity towards human lung adenocarcinoma cell line H1975 with an IC50 value of 11.0 µM, and 14, which contained an active center, -C=N+, exhibited antibacterial activity. An analysis of the relationship between the structures, enzyme inhibitory activity and cytotoxicity of 1-14 revealed that the substituents at C-7 of the isoquinoline nucleus could greatly affect their bioactivity.
Asunto(s)
Alcaloides/farmacología , Antibacterianos/farmacología , Antineoplásicos/farmacología , Aspergillus , Isoquinolinas/farmacología , Proteínas Tirosina Fosfatasas/antagonistas & inhibidores , Alcaloides/química , Animales , Antibacterianos/química , Antineoplásicos/química , Organismos Acuáticos , Línea Celular Tumoral/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Isoquinolinas/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
Simplifusidic acids A-K (1-11), 11 new fusidane-type nortriterpenoids, were isolated from the marine-derived fungus Simplicillium sp. SCSIO 41513. Compound 1 possessed an unprecedented fusidane triterpene skeleton with a 6/6/7/5/5 polycyclic system. Their structures were elucidated by spectroscopic methods, and their absolute configurations were further determined by quantum chemical calculations of ECD spectra, comparison of experimental ECD spectra, and single-crystal X-ray diffraction analysis. Compound 9 showed strong antibacterial activity toward Staphylococcus aureus with an MIC value of 0.078 µg/mL. Their structure-bioactivity relationship was also discussed.
Asunto(s)
Antibacterianos/aislamiento & purificación , Hypocreales/metabolismo , Triterpenos/aislamiento & purificación , Antibacterianos/química , Antibacterianos/farmacología , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-Actividad , Triterpenos/química , Triterpenos/farmacologíaRESUMEN
Three undescribed cyclic lipopeptides maribasins C-E and four undescribed linear peptides aspergillipeptides H-K together with three known analogous maribasins A-B and marihysin A were isolated from the marine gorgonian-associated fungus Aspergillus sp. SCSIO 41501 (Trichocomaceae). Their structures were determined by spectroscopic analysis, and their absolute configurations were further confirmed by Marfey's methods. Maribasins C-E and maribasins A-B showed significant antifungal activity against five phytopathogenic fungal strains with MIC values of 3.12-50 µg/disc. Structure-bioactivity relationship exhibited that the ß-amino fatty acid chain could significantly affect the antifungal activity of this type of cyclic lipopeptides.
Asunto(s)
Antifúngicos , Aspergillus , Antifúngicos/farmacología , Hongos , Estructura Molecular , Péptidos Cíclicos/farmacologíaRESUMEN
One strain many compounds (OSMAC) strategy was an effective method to activate the silent biosynthetic genes of microorganisms. Comparison with our previous investigations on the secondary metabolites of the marine-derived fungus Aspergillus sp. SCSIO 41501, in this study, three new cyclopentenone derivatives, aspergispones A-C (1-3), and five new cyclohexenone derivatives, aspergispones D-H (4-8), together with two known analogues, were further isolated from the fungal strain by altering culture medium compositions. The structures of new compounds were elucidated by extensive spectroscopic analysis. And the absolute configurations of 4 and 7 were further confirmed by single-crystal X-ray diffraction experiments.
Asunto(s)
Aspergillus , Hongos , Ciclopentanos , Estructura MolecularRESUMEN
Three novel andrastin-type meroterpenoids, penicimeroterpenoids A-C (1-3), possessing two unprecedented skeletons consisting of fused 6/5/6/6/7 and 6/5/6/6/4 polycyclic systems, were obtained from the marine-derived fungus Penicillium sp. SCSIO 41512. Their structures were determined by spectroscopic methods, and the absolute configurations were further determined by single-crystal X-ray diffraction analysis for 1 and quantum chemical calculations of ECD spectra for 2 and 3, respectively. A plausible biosynthetic pathway for 1-3 was proposed.
Asunto(s)
Penicillium/química , Terpenos/química , Fenómenos Bioquímicos , Cristalografía por Rayos X , Estructura Molecular , Terpenos/aislamiento & purificaciónRESUMEN
Two new cyclopentapeptides, xylapeptide A (1) with an uncommon L-pipecolinic acid moiety, and xylapeptide B (2) having a common L-proline residue were identified from an associated fungus Xylaria sp. isolated from the Chinese medicinal plant Sophora tonkinensis. Their planar structures were elucidated by a comprehensive analysis of NMR and MS spectroscopic spectra. The absolute configurations were determined by Marfey's method and single-crystal X-ray diffraction (Cu Kα) analysis. Xylapeptide A (1) is the first example of cyclopentapeptide with L-Pip of terrestrial origin and showed strong antibacterial activity against Bacillus subtilis and B. cereus with MIC value of 12.5 µg/mL.