Sesquiterpene Aryl Esters Research Articles

Three Undescribed Protoilludane-Type Sesquiterpene Aryl Esters from Armillaria gallica.

Three previously undescribed protoilludane-type sesquiterpene aryl esters, armillanals A-C (1-3), along with seven known ones (4-10) were obtained from Armillaria gallica Marxm. & Romagn. Compounds 1 and 2 were a rare class of sesquiterpenes featuring the Δ2(3) and Δ12(13)-protoilludane skeleton. Their structures were established by extensive spectroscopic methods. Based on electronic circular dichroism (ECD) calculations, the absolute configurations of three new compounds (1-3) were determined. The anti-inflammatory activity of compounds 1-10 was screened and compound 3 could dose-dependently decrease the level of lactate dehydrogenase, showing IC50 value of 4.525 μM.

5′-O-methyl-14-hydroxyarmillane, a new armillane-type sesquiterpene from cultures of Guyanagaster necrorhiza

Protoilludene-type sesquiterpene aryl esters are a unique and very diverse compound class that were exclusively isolated from members of the genus Armillaria (Agaricomycetes, Physalacriaceae) up to this point. Herein, we describe the isolation and structural characterization of 5′-O-methyl-14-hydroxyarmillane (1), a new armillane-type derivative, that was obtained from submerged cultures of Guyanagaster necrorhiza (CBS 138623) together with the known congeners melleolide G (2), melleolide B (3), and 10-dehydroxy-melleolide B (4). ROESY data and coupling constants assigned the relative configurations of 1, while common absolute configurations were confirmed from comparison of its ECD spectrum to the one of 10-hydroxy-5′-methoxy-6′-chloroarmillane (5). Additionally, the configuration of melleolide G (2) was revised based on observed ROESY correlations. It is the first time that protoilludene-type sesquiterpene aryl esters were isolated from another genus, namely, Guyanagaster, that is closely related to Armillaria. 1–4 were evaluated for their biological activities in a serial dilution assay against several yeast, fungi, and bacteria, as well as in a cytotoxicity assay against different cell lines. Compound 4 was moderately active against Bacillus subtilis, Staphylococcus aureus, and Mucor hiemalis. Furthermore, 1, 3, and 4 showed weak cytotoxic effects against the mouse fibroblast cell line L929 and the cervix carcinoma cell line KB3.1.

Secondary metabolites of six Siberian and Crimean Armillaria species and their in vitro phytotoxicity to pine, larch and poplar

Basidiomycetes Armillaria infect deciduous, coniferous and fruit trees, causing enormous economic damage. The role of secondary metabolites (tricyclic sesquiterpene aryl esters - melleolides) in the life cycle and pathogenesis of Armillaria is under active investigation. To date, not all species of Armillaria have been tested for the biosynthesis of melleolides. We investigated the secondary metabolite profiles of six root-pathogenic species of the genus Armillaria (A. borealis Marxmüller & Korhonen, A. cepistipes Velenovský, A. gallica Marxm, A. mellea (Vahl) P. Kummer, A. sinapina Bérubé & Dessur, A. ostoyae (Romagn.) Herink) distributed in Siberia (South Krasnoyarsk Krai, Republic of Tyva, Republic of Khakassia, Taimyr Peninsula), Russian Far East (Sikhote-Alin) and Crimea (Krymsky National Park, Chatyr-Dag Mountain Lower Plateau). A total of 15 compounds were identified in the metabolome profile. Two compounds (melleolide D and melledonal C) are synthesized by all investigated strains irrespective of their geographic location and host plant. The maximum spectrum of melleolides (7-8 compounds) was found in isolates of A. borealis, A. gallica, A. sinapina, A. ostoyae. In submerged culture, the maximum accumulation of melleolides varied from 2 up to 239 mg l-1. A mixture of melleolide D and melledonal C (1:1) synthesized by the most productive strain A. mellea Cr2-17 was first found to have a phytotoxic action on the growth parameters of the callus culture Populus balsamifera and 10-day-old conifer seedlings. A 0.5% concentration of melleolides caused a credible decrease of P. balsamifera callus raw biomass; a decrease of the viability of Larix sibirica and, which is especially significant, Pinus sylvestris seedlings; inhibition of stem and root growth processes; dechromation of foliage; loss of turgor. The occurrence of a broad range of melleolides in the metabolome profile and two common compounds in all investigated strains, with a phytotoxic action at their sufficiently high concentration, enables considering the synthesis of melleolides by Armillaria fungi as one of the possible mechanisms of their pathogenicity efficiently realized in strains characterized by overproduction of melleolides under natural conditions.

Two new sesquiterpene aryl esters from Armillaria gallica 012m

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.

Plant growth regulators from mushrooms.

Plants interact with fungi in their natural growing environments, and relationships between plants and diverse fungal species impact plants in complex symbiotic, parasitic, and pathogenic ways. Over the past 10 years, we have intensively investigated plant growth regulators produced by mushrooms, and we succeeded in finding various regulators from mushroom-forming fungi: (1) fairy chemicals as a candidate family of new plant hormones from Lepista sordida, (2) agrocybynes A to E from fungus Agrocybe praecox that stimulate strawberry growth, (3) armillariols A to C and sesquiterpene aryl esters from genus Armillaria that are allelopathic and cause Arimillaria root disease, and (4) other plant growth regulators from other mushrooms, such as Stropharia rugosoannulata, Tricholoma flavovirens, Hericium erinaceus, Leccinum extremiorientale, Russula vinosa, Pholiota lubrica and Cortinarius caperatus.

Biosynthesis of Protoilludene Sesquiterpene Aryl Esters by Siberian Strains of the Genus Armillaria Fungi

Secondary metabolites of the basidiomycetes of Armillaria borealis Marxm. and Korhonen, A. cepistipes Velen., A. gallica Marxm., A. ostoyae (Romagn.) Herink, and A. sinapina Berube and Dessur isolated in Southern Siberia (Krasnoyarsk region and Tyva Republic) and in the Far East (Sikhote-Alin) were studied. Metabolites belonging to the class of protoilludene sesquiterpene aryl esters of the melleolides group have been identified in the species A. borealis, A. cepistipes, and A. sinapina. The strains differ in the spectrum of synthesized melleolides. A. borealis strain 74g synthesized a wider range of melleolides than other strains of the species: melleolides B, C, D and H, melledonals B and C, 5'-O-methylmelledonal, 13-hydroxy-5'-O-methylmelledonal, and armillarinin. It was shown that the composition of the medium influenced the amount of synthesized metabolites. All of the studied strains synthesizing melleolides exhibited a toxicogenic and phytopathogenic effect on seeds and seedlings of Picea abies (L.) H. Karst. and Abies sibirica Ledeb. A significant decrease in seed germination energy, laboratory and ground seed germination, the development of the root system of conifer seedlings was revealed. The maximum inhibitory effect was shown by the culture fluid of A. borealis 74g with the greatest amounts and variety of melleolides in the metabolome profile.

Structure, cytotoxic activity and mechanism of protoilludane sesquiterpene aryl esters from the mycelium of Armillaria mellea

Ethnopharmacological relevanceArmillaria mellea (Vahl. ex. Fr.) Karst is an important traditional Chinese medicine used in dispelling wind and removing obstruction in the meridians, and strengthening tendons and bones. Armillaria mellea has been recorded in the book Caobenshiyi which was written by ancestor for the function of suppressing hyderactive liver for calming endogenous wind medicine. The aim of this study is to investigate the cytotoxic activity for liver cell lines (normal and cancerous) of protoilludane sesquiterpene aryl esters from the mycelium of A. mellea. Materials and methodsA systemic fractionation of the mycelium extracts of A. mellea and relative activity mechanisms were studied. ResultsTwo new protoilludane sesquiterpene aryl esters named 5′-methoxy-armillasin (1) and 5-hydroxyl-armillarivin (2) were isolated. In addition, eight known protoilludane sesquiterpene aryl esters armillaridin (3), armillartin (4), armillarin (5), melleolide B (6), armillarilin (7), armillasin (8), armillarigin (9) and melleolide (10) were also isolated from the mycelium of A. mellea. The relative configurations of the two new compounds were confirmed by NOESY spectra. Among ten protoilludane sesquiterpene aryl esters, compounds 2, 3, 4, 7, 8, 9 and 10 were active constituents with highly cytotoxic activity against HepG2 cells (4.95–37.65μg/mL). We reported here for the time, that compound 10 (melleolide) showed anti-tumor ability on hepatoma cell. The relative mechanism was assessed on HepG2 cells. ConclusionsAmong all the ten protoilludane sesquiterpene aryl esters, melleolide (10) showed the best cytotoxic activity for HepG2 cells (4.95μg/mL) and lower activity for L02 cells (16.05μg/mL). Mechanism study showed that melleolide decreased the viability of the cancer cells with varying levels of cleaved-caspase 3, caspase 8, caspase 9, Bax and Ki67 expression. On the other hand, melleolide induced HepG2 cell cycle arrest at the G2/M phase.

Three New Sesquiterpene Aryl Esters from the Mycelium of Armillaria mellea

Three new sesquiterpene aryl esters and eight known compounds were isolated from the EtOH extract of the mycelium of Armillaria mellea. The structures of new compounds were established by analysis of their spectroscopic data. Some of the isolates showed cytotoxicity to a variety of cancer cell lines, including MCF-7, H460, HT-29, and CEM.

Structures and cytotoxicities of three new sesquiterpenes from cultures of Armillaria sp.

Graphical abstractThree new sesquiterpene aryl esters, named 10-dehydroxy-melleoliede B (1), 1-O-formyl-10-dehydroxy-melleoliede B (2) and 10-oxo-melleoliede B (3) together with six known ones (4–9), were isolated from the cultures of Armillaria sp. The structures of the new compounds were elucidated based on the extensive spectroscopic methods. Compounds 1, 2, and 5–9 exhibited moderate cytotoxicities. Electronic Supplementary MaterialSupplementary material is available for this article at 10.1007/s13659-012-0077-1 and is accessible for authorized users.

In vitro cytotoxicity of melleolide antibiotics: Structural and mechanistic aspects

Melleolide sesquiterpene aryl esters are secondary products of the mushroom genus Armillaria. We compared the cytotoxicity of eleven melleolides--five thereof are new natural products--against four human cancer cell lines. Armillaridin, 4-O-methylarmillaridin, and dehydroarmillylorsellinate were most active, at IC(50) = 3.0, 4.1 and 5.0 μM, respectively, against Jurkat T cells for the former two compounds, and K-562 cells for the latter. Dehydroarmillylorsellinate did not inhibit respiration and RNA-synthesis of K-562 cells at 5 μM. However, replication of DNA dropped to 35% after 120 min at this concentration, and translational activity also decreased.

Sesquiterpene aryl esters from Armillaria tabescens

Five new sesquiterpene aryl esters based on the Δ 2, 3-protoilludane keleton were isolated from Armillaria tabescens grown in culture. These were characterized as 4-dehydro-14-hydroxydihydromelleolide, 4-dehydro-dihydromelleolide, 14-hydroxydihydromelleolide, 13-hydroxy-4-methoxymelleolide and 5β,10α-dihydroxy-1-orsellinate-dihydromelleolide. The structures of these compounds was established by collective NMR techniques.

Liquid chromatographic-thermospray mass spectrometric analysis of sesquiterpenes of Armillaria (Eumycota: Basidiomycotina) species

Conventional HPLC analysis of the sesquiterpene aryl esters present in the crude extracts of the pathogenic basidiomycete Armillaria is complicated by difficulties in identification solely on the basis of retention time. On-line coupling of liquid chromatography with thermospray mass spectrometry (LC-TSP-MS) provides a means for their direct detection. Crude extracts of seven Armillaria species were analysed providing a semi-quantitative survey of sesquiterpene aryl ester production within the genus. The distribution of these metabolites and its significance with regard to species differentiation and pathogenicity are discussed. Unknown components were also detected by on-line LC-TSP-MS screening of extracts, facilitating a targeted isolation route.

Armillane, a saturated sesquiterpene ester from Armillaria mellea

Analysis of the mycelial extract of Armillaria mellea (strain 619) has led to the isolation of three new sesquiterpene aryl esters, which have been identified as a protoilludane armillane, and two Δ 2,3-protoilludenes, 10α-hydroxyarmillarin and 4- O-methylarmillaridin. Their structures were deduced on the basis of spectral data and by comparison with related compounds.

Two new sesquiterpene esters from Armillaria mellea

Two new sesquiterpene aryl esters 15-hydroxy-5′- O-methylmelledonal and 5′- O-methylmelledonal, were isolated from the culture broth extract

Melledonal and melledonol, sesquiterpene esters from armillaria mellea

Isolation of two new sesquiterpene aryl esters melledonal (6) and melledonol (8) from culture broth extract of Armillaria mellea are reported. Their structures were deduced from spectral and chemical data.