ABSTRACT
Our screening project, namely, search for new immunomodulatory constituents from Ascomycetous fungi, was guided by the effects on mitogen-induced proliferations of mouse spleen lymphocytes. On the project, the defatted crude extracts from Gelasinospora multiforis, G. heterospora, G. longispora, G. kobi, Diplogelasinospora grovesii, Emericella aurantio-brunnea, Eupenicillium crustaceum, etc., submitted to the solvent partition followed by fractionation with repeated chromatography monitored by immunomodulatory activity to afford many active constituents, of which molecular structures including absolute configurations and immunomodulatory activities were elucidated. All of these immunomodulatory constituents isolated on the project were practically not immunostimulants but immunosuppressants.
Subject(s)
Ascomycota/chemistry , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/pharmacology , Molecular StructureABSTRACT
As Cistus laurifolius has been used traditionally to treat inflammatory and rheumatic disorders, its leaves were tested for prostaglandin (PG) inhibitory and antioxidant activities. The leaf extract showed both activities, i.e., inhibitory effect at 300 microg/ml on PGE1- and E2-induced contractions in guinea pig ileum and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect. The separation guided by the activities shown by these dual assays provided sixteen compounds, 1-16. Known compounds 1-12 and 15 were identified as 3-O-methyl quercetin (1), 3,7-O-dimethyl quercetin (2), genkwanin (3), 3,7-O-dimethyl kaempferol (4), 3,4'-O-dimethyl quercetin (5), apigenin (6), 3,4'-O-dimethyl kaempferol (7), ellagic acid (8), beta-sitosterol-3-O-beta-glucoside (9), quercetin 3-O-alpha-rhamnoside (10), 5-O-p-coumaroyl quinic acid methyl ester (11), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-alpha-l-rhamnopyranoxypropyl)-2-methoxyphenoxy]-1,3-propanediol (12) and 2,3-dihydro-2-(4'-alpha-l-rhamnopyranosyloxy-3'-methoxyphenyl)-3-hydroxymethyl-7-methoxy-5-benzofuranpropanol (15). New lignan glycosides 13 and 14 were determined to be olivil 9-O-beta-D-xyloside and berchemol 9-O-rhamnoside, respectively. Compound 16 was isolated as a 2:1 mixture of two diastereomers, the major one of which was determined to be (7S,8R)-dihydrodehydrodiconiferyl alcohol 9'-O-alpha-L-rhamnoside. The structures were determined by detailed 2D NMR analysis together with NOEDF and CD. PG inhibitory effect was observed in 1, 5, 10, 12 and 16 at 30 microg/ml and antioxidant activity, in 1, 2, 8, 10, 12-14 and 16.
Subject(s)
Antioxidants/pharmacology , Cistus/chemistry , Plants, Medicinal/chemistry , Prostaglandins/pharmacology , Alprostadil/pharmacology , Animals , Antioxidants/isolation & purification , Biphenyl Compounds/antagonists & inhibitors , Biphenyl Compounds/chemistry , Dinoprostone/pharmacology , Flavonoids/isolation & purification , Flavonoids/pharmacology , Guinea Pigs , Hydrazines/antagonists & inhibitors , Hydrazines/chemistry , Ileum/drug effects , Ileum/physiology , Male , Molecular Structure , Muscle Contraction/drug effects , Oxidation-Reduction/drug effects , Picrates , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Leaves/chemistry , TurkeyABSTRACT
Investigation of the inhibitory fraction of Leucas aspera on prostaglandin-induced contraction in guinea pig ileum provided four new diterpenes, leucasperones A (1) and B (2) and leucasperols A (3) and B (4), and three new isopimarane glycosides, leucasperosides A, B, and C (5-7), together with the known compounds asperphenamate, maslinic acid, (-)-isololiolide, and linifolioside. The structures of the compounds were determined by detailed spectroscopic analysis. The configurations of 1 and 2 and the acetylated derivatives of 3 and 4 were determined by differential NOE analysis and CD data. Leucasperone A (1), leucasperosides A (5) and B (6), and linifolioside showed inhibition of prostaglandin-induced contractions.
Subject(s)
Diterpenes , Glycosides , Lamiaceae/chemistry , Plants, Medicinal/chemistry , Prostaglandin Antagonists , Animals , Antioxidants/pharmacology , Bangladesh , Biphenyl Compounds , Diterpenes/chemistry , Diterpenes/isolation & purification , Diterpenes/pharmacology , Glycosides/chemistry , Glycosides/isolation & purification , Glycosides/pharmacology , Guinea Pigs , Ileum/drug effects , Male , Molecular Structure , Picrates/pharmacology , Prostaglandin Antagonists/chemistry , Prostaglandin Antagonists/isolation & purification , Prostaglandin Antagonists/pharmacologyABSTRACT
Five metabolites tentatively called GS-1 (1)-5 (5) from Gelasinospora santi-florii, and four tentatively called EQ-4 (6), EQ-6 (7)-8 (9) together with 1-4 from Emericella quadrilineata have been isolated in a screening study on immunomodulatory fungal constituents. Among these nine metabolites, EQ-7 and 8 have been unknown. This time, the structures of GS-4 which has previously been isolated, EQ-7, and -8 have been determined to be (4R,4aS,9aR)-1,9a-dihydronidulalin A (4), (4S,4aR,9aR)-4a-carbomethoxy-1,4,4a,9a-tetrahydro-4,8-dihydroxy-6-methylxanthone (8), and 9-hydroxymicroperfuranone (9), respectively, and the six other metabolites have been identified. On bioassay, a dihydroxanthone, nidulalin A (1), a hexaketide, sordarial (5), and a xanthone, pinselin (7) have displayed significant immunosuppressive activities. The structure-activity relationships of these constituents have also been discussed.
Subject(s)
Ascomycota/chemistry , Cell Proliferation/drug effects , Immunosuppressive Agents/pharmacology , Xanthones/pharmacology , Animals , Cells, Cultured , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/isolation & purification , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Mice , Spleen/cytology , Spleen/metabolism , Structure-Activity Relationship , Xanthones/chemistry , Xanthones/isolation & purificationABSTRACT
In a screening study on immunomodulatory fungal constituents, eleven new 2-pyrones tentatively named TT-1 (1), and TT-2-11 (2-11) have been isolated from a Fungi Imperfecti, Trichurus terrophilus, and designated rasfonin (1), and trichurusin B-K (2-11), respectively. Compounds 1-4 exhibited considerably high immunosuppressive activities, and compounds 8-11 have shown moderate ones. The structure-activity relationships of these constituents have also been discussed.
Subject(s)
Immunologic Factors/isolation & purification , Pyrones/isolation & purification , Chromatography, High Pressure Liquid , Drug Screening Assays, Antitumor , Immunologic Factors/chemistry , Immunologic Factors/pharmacology , Pyrones/chemistry , Pyrones/pharmacology , Spectrum Analysis/methodsABSTRACT
In a screening study on immunomodulatory fungal metabolites, three known anthraquinones, carviolin (roseo-purpurin) (1), 1-O-methylemodin (2), omega-hydroxyemodin (citreorosein) (4), and a new anthraquinone, omega-acetylcarviolin (3), together with a known steroid, ergosta-4,6,8(14),22-tetraen-3-one (5) and a new steroid, 25-hydroxyergosta-4,6,8(14),22-tetraen-3-one (6) were isolated from an Ascomycete, Zopfiella longicaudata, and found to have moderate immunosuppressive activities. The structure-activity relationships of these metabolites are discussed.
Subject(s)
Ascomycota/chemistry , Ergosterol/analogs & derivatives , Immunosuppressive Agents/isolation & purification , Anthraquinones/chemistry , Anthraquinones/isolation & purification , Anthraquinones/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Emodin/analogs & derivatives , Emodin/isolation & purification , Emodin/pharmacology , Ergosterol/chemistry , Ergosterol/isolation & purification , Ergosterol/pharmacology , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/pharmacology , Magnetic Resonance Spectroscopy , Mass Screening , Structure-Activity RelationshipABSTRACT
A screening study focusing on immunomodulatory activity of the EtOAc extract of an Ascomycete, Chaetomium seminudum, has afforded a known epipolythiodioxopiperazine, chetomin (1), together with three new chetomin-related metabolites named chetoseminudins A (2), B (3), and C (4). Among these four metabolites, 1 and 2 have been deduced as the immunosuppressive features of this fungus.
Subject(s)
Adjuvants, Immunologic/isolation & purification , Anti-Bacterial Agents/isolation & purification , Chaetomium/chemistry , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Disulfides , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/pharmacology , Indole Alkaloids , Japan , Lymphocytes/drug effects , Mice , Molecular Structure , Spleen/cytologyABSTRACT
Two new pregnane alkaloids, wrightiamines A (1) and B (2), were isolated from the extract of the tropical Apocynaceous plant Wrightia javanica collected in Thailand, and their structures were elucidated by spectral data. Wrightiamine B (2) was preparaed from 3beta-hydroxy-5alpha-pregnan-20-one to establish the configuration of the C-20 position as S. Wrightiamine A (1) exhibited cytotoxic activity against vincristine-resistant murine leukemia P388 cells.
Subject(s)
Antineoplastic Agents/isolation & purification , Apocynaceae/chemistry , Pregnanes/isolation & purification , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Survival/drug effects , Drug Resistance, Neoplasm , Leukemia P388/drug therapy , Magnetic Resonance Spectroscopy , Mice , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Leaves/chemistry , Pregnanes/chemistry , Pregnanes/pharmacology , Tumor Cells, CulturedABSTRACT
According to the traditional usage of the plant for antiinflammation and analgesia, Leucas aspera was tested for its prostaglandin (PG) inhibitory and antioxidant activities. The extract showed both activities, i.e., inhibition at 3 x 10(-4) g/ml against PGE(1)- and PGE(2)-induced contractions in guinea pig ileum and a 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect. The separation guided by the activities in these dual assay methods provided eight lignans and four flavonoids, LA-1- -12, among which LA-1- -7 and LA-10- -12 were identified as nectandrin B, meso-dihydroguaiaretic acid, macelignan, acacetin, apigenin 7-O-[6"-O-(p-coumaroyl)-beta-D-glucoside], chrysoeriol, apigenin, erythro-2-(4-allyl-2, 6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)propan-1-ol, myristargenol B, and machilin C, respectively. LA-8 was determined to be (-)-chicanine, the new antipode of the (+) compound, by spectroscopic methods including CD and ORD. Chiral-HPLC analysis of LA-9 showed that it was a mixture of two enantiomers, (7R, 8R)- and (7S, 8S)-licarin A. All of these components were first isolated from L. aspera. PG inhibition was observed in LA-1, LA-2, and LA-5, and antioxidant activity in LA-1- -3 and LA-8- -12.
Subject(s)
Antioxidants/chemistry , Plants, Medicinal/chemistry , Prostaglandin Antagonists/chemistry , Alprostadil/antagonists & inhibitors , Alprostadil/pharmacology , Animals , Antioxidants/isolation & purification , Bangladesh , Biphenyl Compounds , Chromatography, Thin Layer , Circular Dichroism , Dinoprostone/antagonists & inhibitors , Dinoprostone/pharmacology , Guinea Pigs , Ileum/drug effects , In Vitro Techniques , Magnetic Resonance Spectroscopy , Male , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Picrates/chemistry , Plant Extracts/chemistry , Plant Leaves/chemistry , Polarography , Prostaglandin Antagonists/isolation & purificationABSTRACT
A screening study focusing on monoamine oxidase inhibitory activity on the EtOAc extract of an Ascomycete Chaetomium quadrangulatum, which previously gave five unique chromones possessing this activity (chaetoquadrins A-E (1-5)), this time afforded six new constituents termed chaetoquadrins F-K (6-11) in addition to 1-5. The structures of 6-11 have been deduced on the basis of spectral and chemical data, and 7 and 8 have shown appreciable monoamine oxidase inhibitory activity.
Subject(s)
Chaetomium/chemistry , Monoamine Oxidase Inhibitors/chemistry , Monoamine Oxidase Inhibitors/isolation & purification , Drug Evaluation, Preclinical/methods , Monoamine Oxidase Inhibitors/pharmacologyABSTRACT
Three new natural onoceranoid triterpenes, lansionic acid (1), 3beta-hydroxyonocera-8(26),14-dien-21-one (2), and 21alpha-hydroxyonocera-8(26),14-dien-3-one (3), were isolated from the fruit peel of Lansium domesticum together with two known triterpenoids (4 and 5), and their structures were elucidated from spectral data. These triterpenoids exhibited mild toxicity against brine shrimp (Artemia salina).
Subject(s)
Meliaceae/chemistry , Triterpenes/isolation & purification , Animals , Artemia/drug effects , Fruit/chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Spectrophotometry, Infrared , Thailand , Triterpenes/chemistry , Triterpenes/pharmacologyABSTRACT
Five novel chromones (1,4-benzopyran-4-ones), among which three are tetracyclic and one contains a sulfonyl group, have been isolated from an Ascomycete, Chaetomium quadrangulatum, as monoamine oxidase inhibitory features, and named chaetoquadrins A (1)-E (5).