ABSTRACT
Two new heterodimeric sesquiterpenes, sterhirsutins C (1) and D (2), along with eight new sesquiterpenoid derivatives, sterhirsutins E--L (3-10), were isolated from the culture of Stereum hirsutum. The absolute configuration of 1 was assigned by a single-crystal X-ray diffraction experiment. Compounds 1 and 2 possessed an unprecedented chemical skeleton with a 5/5/5/6/9/4 fused ring system. Compound 10 is the first sesquiterpene coupled with a xanthine moiety. Compounds 1-10 showed cytotoxicity against K562 and HCT116 cell lines. Compound 9 induced autophagy in HeLa cells. Compound 5 inhibited the activation of IFNß promoter in Sendai virus infected cells.
Subject(s)
Antineoplastic Agents/chemistry , Basidiomycota/chemistry , Fungi/chemistry , HCT116 Cells/chemistry , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/pharmacology , Interferon-beta/chemistry , Sendai virus/chemistry , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Xanthine/chemistry , Antineoplastic Agents/pharmacology , Crystallography, X-Ray , HCT116 Cells/drug effects , HeLa Cells , Humans , Interferon-beta/pharmacology , K562 Cells , Magnetic Resonance Spectroscopy , Molecular Structure , Sendai virus/drug effects , TibetABSTRACT
Four new ambuic acid derivatives (1-4), and four known derivatives (5-8), were isolated from the solid culture of a plant pathogenic fungus Pestalotiopsis neglecta. Their structures were elucidated by extensive NMR experiments. The absolute configuration of the C-16 secondary alcohol in 1 was deduced via the CD data of the in situ formed [Rh2(OCOCF3)4] complex with the acetonide derivative of 1. The absolute configuration in 3 was assigned by comparison of the experimental and simulated electronic circular dichroism (ECD) spectrum. The NMR data of compound 5 was reported for the first time. In the nitric oxide (NO) inhibition assay, compounds 4, 6 and 7 showed inhibitory activity against the NO production in the lipopolysaccharide (LPS)-induced macrophage with IC50 values of 88.66, 11.20, and 20.80 µM, respectively.
Subject(s)
Ascomycota/metabolism , Cyclohexanones/metabolism , Cyclohexanones/pharmacology , Nitric Oxide/antagonists & inhibitors , Cyclohexanones/chemistry , Inhibitory Concentration 50 , Magnetic Resonance SpectroscopyABSTRACT
A new cochlioquinone derivative, cochlioquinone F (1), as well as three known compounds, anhydrocochlioquinone A (2), isocochlioquinone A (3), and isocochlioquinone C (4), were isolated from the PDB (potato dextrose broth) culture of the phytopathogenic fungus Bipolaris luttrellii. The structure of 1 was elucidated on the basis of NMR techniques. The apoptosis-inducing effects of compounds 1-4 were evaluated against HCT116 cancer cells. Compoundâ 2 exhibited the strongest activity in inducing apoptosis on HCT116 cells within the range of 10-30â µM. In addition, the caspase activation, the release of cytochrome c from mitochondria, and the downregulation of Bcl-2 protein in HCT116 cells treated with compoundâ 2 were detected.
Subject(s)
Apoptosis/drug effects , Ascomycota/chemistry , Benzoquinones/pharmacology , HCT116 Cells , Humans , Magnetic Resonance Spectroscopy , Spectrometry, Mass, Electrospray IonizationABSTRACT
Two new heterodimeric sesquiterpenes, sterhirsutins A (1) and B (2), and two new sesquiterpenes, hirsutic acids D-E (3 and 4), were identified from the culture of Stereum hirsutum. The absolute configurations in 1 and 2 were confirmed by single-crystal X-ray diffraction experiments and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 are likely biosynthesized from a hirsutane-type sesquiterpene and α-humulene by a hetero-Diels-Alder cycloaddition. Compounds 1-4 showed cytotoxicity against K562 and HCT116 cell lines.
Subject(s)
Antineoplastic Agents/isolation & purification , Basidiomycota/chemistry , Sesquiterpenes/isolation & purification , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Circular Dichroism , Crystallography, X-Ray , HCT116 Cells , Humans , K562 Cells , Molecular Structure , Monocyclic Sesquiterpenes , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , TibetABSTRACT
Nine new isoprenylated depsides, sterenins E-M (1-9), as well as five known compounds (10-14), were isolated from the solid culture of Stereum hirsutum. The structures of the new compounds were elucidated by spectroscopic methods. Their inhibitory activities against yeast α-glucosidase were evaluated in vitro. Compounds 1-4 and 7-14 showed inhibitory activities with IC50 values of 7.62, 3.06, 6.03, 22.70, 36.64, 13.09, 27.52, 25.10, 12.32, 3.31, 23.82, and 14.17 µM, respectively. Compounds 5 and 6 showed no inhibitory activities with IC50 values higher than 50 µM. Therefore, the culture of S. hirsutum and its secondary metabolites could have a potential usage for the development of hypoglycemic drugs.
Subject(s)
Agaricales/chemistry , Depsides/pharmacology , Glycoside Hydrolase Inhibitors/pharmacology , Terpenes/pharmacology , Depsides/chemistry , Depsides/isolation & purification , Fruiting Bodies, Fungal/chemistry , Fungal Proteins/metabolism , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Molecular Structure , Terpenes/chemistry , Terpenes/isolation & purification , alpha-Glucosidases/drug effectsABSTRACT
Coicenals A-C (1-3) possessing a previously undescribed 10-(sec-butyl)-6-hydroxy-1,7,9-trimethyl-1,6,7,8,9,9a-hexahydro-1,4-methanobenzo[d]oxepin-2(4H)-ylidene)acetaldehyde skeleton and coicenal D (4) with a new 2-(sec-butyl)-5-hydroxy-1,6,8-trimethyl-2,5,6,7,8,8a-hexahydro-1H-4a,1-(epoxymethano)naphthalen-10-ylidene)acetaldehyde skeleton were isolated from the solid culture of the plant pathogenic fungus Bipolaris coicis. The absolute configurations in 1 and 4 were assigned by electronic circular dichroism (ECD) calculations. Compounds 1 and 2 were transformed into 4 and 5 by treatment with acetyl chloride, respectively. Compounds 1-4 showed moderate inhibitory activity against NO release with IC50 values of 16.34 ± 1.12, 23.55 ± 1.37, 10.82 ± 0.83, and 54.20 ± 2.82 µM, respectively.
Subject(s)
Diterpenes/chemistry , Fungi/chemistry , Animals , Diterpenes/isolation & purification , Diterpenes/pharmacology , Inhibitory Concentration 50 , Molecular Structure , PhylogenyABSTRACT
A new ophiobolin derivative, 3-anhydro-6-hydroxy-ophiobolin A (1), as well as two known ophiobolin derivatives 3-anhydro-ophiobolin A (2) and 3-anhydro-6-epi-ophiobolin A (3) were isolated from the PDB culture of a phytopathogenic fungus Bipolaris oryzae. The structure of 1 was elucidated through 2D NMR and other spectroscopic techniques. Compound 1 exhibited strong antimicrobial activity against Bacille Calmette-Guerin, Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus with MIC value of 12.5 µg/mL, and potent antiproliferative activity against cell lines HepG2 and K562 with IC50 of 6.49 µM and 4.06 µM, respectively. Further studies on the cytotoxicity of compound 1 against K562 cells demonstrated that it induced apoptosis, observed by flow cytometric method. Preliminary structure-activity relationships of these ophiobolins and the mechanism of apoptosis induced by 1 were analyzed.