Sesquiterpenes are the major pharmacodynamic components of agarwood,a precious traditional Chinese medicine obtained from the resinous portions of Aquilaria sinensis trees that form in response to environmental stress...Sesquiterpenes are the major pharmacodynamic components of agarwood,a precious traditional Chinese medicine obtained from the resinous portions of Aquilaria sinensis trees that form in response to environmental stressors.To characterize the sesquiterpene synthases responsible for sesquiterpene production in A.sinensis,a bioinformatics analysis of the genome of A.sinensis identifi ed six new terpene synthase genes,and 16 sesquiterpene synthase genes were identifi ed as type TPS-a in a phylogenetic analysis.The expression patterns for eight of the sesquiterpene synthase genes after treatment with various hormones or hydrogen peroxide were analyzed by real-time quantitative PCR.The results suggest that 100μM methyl jasmonate,ethephon,(±)-abscisic acid or hydrogen peroxide could be eff ective short-term eff ectors to increase the expression of sesquiterpene synthase genes,while 1 mM methyl salicylate may have long-term eff ects on increasing the expression of specifi c sesquiterpene synthase genes(e.g.,As-SesTPS,AsVS,AsTPS12 and AsTPS29).The expression changes in these genes under various conditions refl ected their specifi c roles during abiotic or biotic stresses.Heterologous expression of a novel A.sinensis sesquiterpene synthase gene,AsTPS2,in Escherichia coli produced a major humulene product,so AsTPS2 is renamed AsHS1.AsHS1 is diff erent from ASS1,AsSesTPS,and AsVS,for mainly producingα-humulene.Based on the predicted space conformation of the AsHS1 model,the small ligand molecule may bind to the free amino acid by hydrogen bonding for the catalytic function of the enzyme,while the substrate farnesyl diphosphate(FPP)probably binds to the free amino acid on one side of the RxR motif.Arg450,Asp453,Asp454,Thr457,and Glu461 from the NSE/DTE motif and D307 and D311 from the DDxxD motif were found to form a polar interaction with two Mg^(2+)clusters by docking.The Mg^(2+)-bound DDxxD and NSE/DTE motifs and the free RXR motif are jointly directed into the catalytic pocket of AsHS1.Comparison of the tertiary structural models of AsHS1 with ASS1 showed that they diff ered in structures in several positions,such as surrounding the secondary catalytic pocket,which may lead to diff erences in catalytic products.Based on the results,biosynthetic pathways for specifi c sesquiterpenes such asα-humulene in A.sinensis are proposed.This study provides novel insights into the functions of the sesquiterpene synthases of A.sinensis and enriches knowledge on agarwood formation.展开更多
A new sesquiterpene lactone eupatoranolide was isolated from the flowers of Eupatorium adenophorum. its structure was elucidated as 26-acetoxy-(7α. 9βH)-3.6(11)cadinadien-12(7)-olide by spectral analysis.
A new sesquiterpene lactone, strychnilactone (1), together with five known sesquite- rpenoids, linderane (2), lindenenol (3), linderalactone (4), hydroxylindestenolide (5), pseudoneo- linderane (6) have been isolated ...A new sesquiterpene lactone, strychnilactone (1), together with five known sesquite- rpenoids, linderane (2), lindenenol (3), linderalactone (4), hydroxylindestenolide (5), pseudoneo- linderane (6) have been isolated from the extracts of Supercritical Fluid Extraction of Lindera strychnifolia. The structure of the new compound was elucidated by means of spectroscopic analysis. And the relative configuration of 1 was assigned on the basis of NOE analysis.展开更多
Two new β-dihydroagarofuran sesquiterpenes were isolated from Euonymus phellomana Loes. and their structures were established on the basis of spectral analysis.
One new sesquiterpene polyol ester named angulatin C was isolated from the root barkof Celastrus angulalus along with a known compound, angulatin B.Their structures wereelucidated on the basis of spectral analysis.
A new sesquiterpene polyol ester was isolated from the leaves of Celastrus angulatus. itsstructure was determined as 1 6. 2 6. 9 a-triacetoxy-8 a-(a-hydroxyl-isobutyryloxy)-15-benzoyloxy-4 a-hydroxy-dihydroagarofuran ...A new sesquiterpene polyol ester was isolated from the leaves of Celastrus angulatus. itsstructure was determined as 1 6. 2 6. 9 a-triacetoxy-8 a-(a-hydroxyl-isobutyryloxy)-15-benzoyloxy-4 a-hydroxy-dihydroagarofuran by means of NMR. MS and IR spectral analysis.Preliminary biological study on antitumor activity revealed that this compound showed strongnonselective cytotoxicity against four of the NCI panel cell lines.展开更多
Three new humulane-type sesquiterpenes,antrodols A–C(1–3),were isolated from cultures of the fungus Antrodiella albocinnamomea.Their structures were elucidated on the basis of extensive spectroscopic analysis.Antrod...Three new humulane-type sesquiterpenes,antrodols A–C(1–3),were isolated from cultures of the fungus Antrodiella albocinnamomea.Their structures were elucidated on the basis of extensive spectroscopic analysis.Antrodols A–C(1–3)are first examples of humulane-type sesquiterpenes isolated from cultures of higher fungi,and antrodol A(1)was the first report of humulane-type sesquiterpene with a methyl rearranged at C-3.All compounds were evaluated in the enzyme inhibition assay against two protein-tyrosine phosphatases(PTPs):MEG2 and PTP1Bc.展开更多
Two novel sesquilerpene diglycosides named dictamnosides F 1 and G 2 were isolated trom methanol extract of the root bark of Dictanmus dasycarpus. Their structures were determined on the basis of spcctroscopic and che...Two novel sesquilerpene diglycosides named dictamnosides F 1 and G 2 were isolated trom methanol extract of the root bark of Dictanmus dasycarpus. Their structures were determined on the basis of spcctroscopic and chemical analysis.展开更多
Two new steroids,3a,17a,19,20-tetrahydroxy-4a-methylpregn-8-ene(1)and 3a,12a,17a,20-tetrahydroxy-4amethylpregn-8-ene(2)and three new sesquiterpenoids,12-hydroxy-a-cadinol(3),3a,12-dihydroxy-d-cadinol(4),and 3a,6a-dih...Two new steroids,3a,17a,19,20-tetrahydroxy-4a-methylpregn-8-ene(1)and 3a,12a,17a,20-tetrahydroxy-4amethylpregn-8-ene(2)and three new sesquiterpenoids,12-hydroxy-a-cadinol(3),3a,12-dihydroxy-d-cadinol(4),and 3a,6a-dihydroxyspiroax-4-ene(5),have been isolated from cultures of the fungus Phellinus igniarius.Their structures were characterized based on extensive spectroscopic data.In preliminary in vitro assays,compounds 3 and 4 exhibited the vascular-activities against phenylephrine-induced vasoconstriction with the relaxing rates of 11.0%and 7.0%at 3910-4 M,respectively.展开更多
Three cDNA clones encoding δ-guaiene synthase, a sesquiterpene cyclase, were isolated from tissue cultures of Aquilaria microcarpa, and data mining analysis of the orthologous genes suggested that 10 and 9 amino acid...Three cDNA clones encoding δ-guaiene synthase, a sesquiterpene cyclase, were isolated from tissue cultures of Aquilaria microcarpa, and data mining analysis of the orthologous genes suggested that 10 and 9 amino acid residues of N- and C-terminal ends of the translated products of these clones remained undefined. The recombinant enzyme proteins, to which the putative missing Nand C-terminal amino acid sequences (MSSAKLGSAS and ALLRHAIEI, respectively) were ligated, exhibited the catalytic activities of sesquiterpene biosynthesis. Among these three δ-guaiene synthases, two isoforms were capable of liberating α-guaiene, δ-guaiene, β-elemene plus α-humulene as a minor product, while remaining one isoenzyme generated α-, δ-guaiene and β-elemene but not α-humulene. Although the enzyme protein solely lacking in the N-terminal 10 amino acid residues was capable of synthesizing the sesquiterpenoids, the protein without 9 amino acids at Cterminal did not exhibit the catalytic activity. These results suggest that two types of δ-guaiene synthase;α-, δ-guaiene, β-elemene-producing type, and α-, δ-guaiene, β-elemene plus α-humulene-producing type;concomitantly occur in A. microcarpa cell cultures, and several amino acid residues at C-terminal of the synthase protein are essential to exhibit the catalytic activities as the sesquiterpene cyclase.展开更多
Two new eremophilane sesquiterpenes 3β-angeloyloxy-8α-hydroxy-6β-methoxy eremophil-7 (11), 9 (10)-dien-8, 12-olide (1) and 3β-angeloyloxy-6β, 8α-dihydroxy-eremophi-7 (11), 9 (10)-dien-8, 12-olide (2) were isolat...Two new eremophilane sesquiterpenes 3β-angeloyloxy-8α-hydroxy-6β-methoxy eremophil-7 (11), 9 (10)-dien-8, 12-olide (1) and 3β-angeloyloxy-6β, 8α-dihydroxy-eremophi-7 (11), 9 (10)-dien-8, 12-olide (2) were isolated from Cacalia ainsliaeflora. Their structures were established by spectroscopic methods and 2D NMR experiments.展开更多
Two new β-dihydroagarofuran sesquiterpene polyol esters were isolated from Celastrus paniculatus, subsp. paniculatus.Their Structures were deduced on the basis of spectral analyses including 2D NMR. CO2 supercritical...Two new β-dihydroagarofuran sesquiterpene polyol esters were isolated from Celastrus paniculatus, subsp. paniculatus.Their Structures were deduced on the basis of spectral analyses including 2D NMR. CO2 supercritical fluid was used in separation.展开更多
Three 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 Armillari...Three 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.展开更多
This study evaluated toxic efficacy of Eupatorium adenophorum extracts,against the Kunming mice.In acute study,we firstly tested median lethal dose(LD50)in mice of three cadinene sesquiterpenes 2-deoxo-2-(acetyloxy)-9...This study evaluated toxic efficacy of Eupatorium adenophorum extracts,against the Kunming mice.In acute study,we firstly tested median lethal dose(LD50)in mice of three cadinene sesquiterpenes 2-deoxo-2-(acetyloxy)-9-oxoageraphorone(DAOA),9-oxo-agerophorone(OA)and 9-oxo-10,11-dehydro-agerophorone(ODA)from Eupatorium adenophorum(Ea).DAOA(215–4640 mg/kg BW,given orally)showed lowest LD50 at 926 mg/kg BW for male mice in contrast with OA(1470 mg/kg BW)and ODA(1470 mg/kg BW).In sub-acute study,repeated doses(75–300 mg/kg BW,for 7 days)of DAOA/OA increased blood parameters,liver and spleen index in dose dependent relationship,along with decrease in thymus index.The blood biochemical and histopathological examination showed that DAOA/OA dose 300 mg/kg BW significantly causes pathological changes of hepatic lobules and hepatocytes,which are consistent with cholestasis and hepatic injury.75 mg/kg dose of DAOA/OA was found to be approximately/totally safe over the span of 7 days treatment showing no change in all above described parameters.Cadinene sesquiterpenes guarantee low risk to environment as a type of low toxic botanical components,which may find potential application in biopesticides development field.展开更多
基金supported by the National Natural Science Foundation of China(81773844).
文摘Sesquiterpenes are the major pharmacodynamic components of agarwood,a precious traditional Chinese medicine obtained from the resinous portions of Aquilaria sinensis trees that form in response to environmental stressors.To characterize the sesquiterpene synthases responsible for sesquiterpene production in A.sinensis,a bioinformatics analysis of the genome of A.sinensis identifi ed six new terpene synthase genes,and 16 sesquiterpene synthase genes were identifi ed as type TPS-a in a phylogenetic analysis.The expression patterns for eight of the sesquiterpene synthase genes after treatment with various hormones or hydrogen peroxide were analyzed by real-time quantitative PCR.The results suggest that 100μM methyl jasmonate,ethephon,(±)-abscisic acid or hydrogen peroxide could be eff ective short-term eff ectors to increase the expression of sesquiterpene synthase genes,while 1 mM methyl salicylate may have long-term eff ects on increasing the expression of specifi c sesquiterpene synthase genes(e.g.,As-SesTPS,AsVS,AsTPS12 and AsTPS29).The expression changes in these genes under various conditions refl ected their specifi c roles during abiotic or biotic stresses.Heterologous expression of a novel A.sinensis sesquiterpene synthase gene,AsTPS2,in Escherichia coli produced a major humulene product,so AsTPS2 is renamed AsHS1.AsHS1 is diff erent from ASS1,AsSesTPS,and AsVS,for mainly producingα-humulene.Based on the predicted space conformation of the AsHS1 model,the small ligand molecule may bind to the free amino acid by hydrogen bonding for the catalytic function of the enzyme,while the substrate farnesyl diphosphate(FPP)probably binds to the free amino acid on one side of the RxR motif.Arg450,Asp453,Asp454,Thr457,and Glu461 from the NSE/DTE motif and D307 and D311 from the DDxxD motif were found to form a polar interaction with two Mg^(2+)clusters by docking.The Mg^(2+)-bound DDxxD and NSE/DTE motifs and the free RXR motif are jointly directed into the catalytic pocket of AsHS1.Comparison of the tertiary structural models of AsHS1 with ASS1 showed that they diff ered in structures in several positions,such as surrounding the secondary catalytic pocket,which may lead to diff erences in catalytic products.Based on the results,biosynthetic pathways for specifi c sesquiterpenes such asα-humulene in A.sinensis are proposed.This study provides novel insights into the functions of the sesquiterpene synthases of A.sinensis and enriches knowledge on agarwood formation.
文摘A new sesquiterpene lactone eupatoranolide was isolated from the flowers of Eupatorium adenophorum. its structure was elucidated as 26-acetoxy-(7α. 9βH)-3.6(11)cadinadien-12(7)-olide by spectral analysis.
文摘A new sesquiterpene lactone, strychnilactone (1), together with five known sesquite- rpenoids, linderane (2), lindenenol (3), linderalactone (4), hydroxylindestenolide (5), pseudoneo- linderane (6) have been isolated from the extracts of Supercritical Fluid Extraction of Lindera strychnifolia. The structure of the new compound was elucidated by means of spectroscopic analysis. And the relative configuration of 1 was assigned on the basis of NOE analysis.
文摘Two new β-dihydroagarofuran sesquiterpenes were isolated from Euonymus phellomana Loes. and their structures were established on the basis of spectral analysis.
文摘One new sesquiterpene polyol ester named angulatin C was isolated from the root barkof Celastrus angulalus along with a known compound, angulatin B.Their structures wereelucidated on the basis of spectral analysis.
文摘A new sesquiterpene polyol ester was isolated from the leaves of Celastrus angulatus. itsstructure was determined as 1 6. 2 6. 9 a-triacetoxy-8 a-(a-hydroxyl-isobutyryloxy)-15-benzoyloxy-4 a-hydroxy-dihydroagarofuran by means of NMR. MS and IR spectral analysis.Preliminary biological study on antitumor activity revealed that this compound showed strongnonselective cytotoxicity against four of the NCI panel cell lines.
基金National Natural Science Foundation of China(U1132607,81373289,81102346)Youth Innovation Promotion Association of CAS(2011312D11019).
文摘Three new humulane-type sesquiterpenes,antrodols A–C(1–3),were isolated from cultures of the fungus Antrodiella albocinnamomea.Their structures were elucidated on the basis of extensive spectroscopic analysis.Antrodols A–C(1–3)are first examples of humulane-type sesquiterpenes isolated from cultures of higher fungi,and antrodol A(1)was the first report of humulane-type sesquiterpene with a methyl rearranged at C-3.All compounds were evaluated in the enzyme inhibition assay against two protein-tyrosine phosphatases(PTPs):MEG2 and PTP1Bc.
文摘Two novel sesquilerpene diglycosides named dictamnosides F 1 and G 2 were isolated trom methanol extract of the root bark of Dictanmus dasycarpus. Their structures were determined on the basis of spcctroscopic and chemical analysis.
基金the National Natural Sciences Foundation of China(U1132607,81102346)Natural Sciences Foundation of Yunnan Province(2011FB099).
文摘Two new steroids,3a,17a,19,20-tetrahydroxy-4a-methylpregn-8-ene(1)and 3a,12a,17a,20-tetrahydroxy-4amethylpregn-8-ene(2)and three new sesquiterpenoids,12-hydroxy-a-cadinol(3),3a,12-dihydroxy-d-cadinol(4),and 3a,6a-dihydroxyspiroax-4-ene(5),have been isolated from cultures of the fungus Phellinus igniarius.Their structures were characterized based on extensive spectroscopic data.In preliminary in vitro assays,compounds 3 and 4 exhibited the vascular-activities against phenylephrine-induced vasoconstriction with the relaxing rates of 11.0%and 7.0%at 3910-4 M,respectively.
文摘Three cDNA clones encoding δ-guaiene synthase, a sesquiterpene cyclase, were isolated from tissue cultures of Aquilaria microcarpa, and data mining analysis of the orthologous genes suggested that 10 and 9 amino acid residues of N- and C-terminal ends of the translated products of these clones remained undefined. The recombinant enzyme proteins, to which the putative missing Nand C-terminal amino acid sequences (MSSAKLGSAS and ALLRHAIEI, respectively) were ligated, exhibited the catalytic activities of sesquiterpene biosynthesis. Among these three δ-guaiene synthases, two isoforms were capable of liberating α-guaiene, δ-guaiene, β-elemene plus α-humulene as a minor product, while remaining one isoenzyme generated α-, δ-guaiene and β-elemene but not α-humulene. Although the enzyme protein solely lacking in the N-terminal 10 amino acid residues was capable of synthesizing the sesquiterpenoids, the protein without 9 amino acids at Cterminal did not exhibit the catalytic activity. These results suggest that two types of δ-guaiene synthase;α-, δ-guaiene, β-elemene-producing type, and α-, δ-guaiene, β-elemene plus α-humulene-producing type;concomitantly occur in A. microcarpa cell cultures, and several amino acid residues at C-terminal of the synthase protein are essential to exhibit the catalytic activities as the sesquiterpene cyclase.
基金This work was supported by the National Natural Sciencc Foundation of China No.29972017the Foundation of the Ministry of Education of China for Doctoral Program No.98073003
文摘Two new eremophilane sesquiterpenes 3β-angeloyloxy-8α-hydroxy-6β-methoxy eremophil-7 (11), 9 (10)-dien-8, 12-olide (1) and 3β-angeloyloxy-6β, 8α-dihydroxy-eremophi-7 (11), 9 (10)-dien-8, 12-olide (2) were isolated from Cacalia ainsliaeflora. Their structures were established by spectroscopic methods and 2D NMR experiments.
文摘Two new β-dihydroagarofuran sesquiterpene polyol esters were isolated from Celastrus paniculatus, subsp. paniculatus.Their Structures were deduced on the basis of spectral analyses including 2D NMR. CO2 supercritical fluid was used in separation.
基金supported by the National Basic Research Program of China(973 Program,2009CB522300)the National Natural Sciences Foundation of China(30830113,U1132607).
文摘Three 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.
基金Special Nonprofit Agricultural Industrial Research Fund(20080321,201103027)of China.
文摘This study evaluated toxic efficacy of Eupatorium adenophorum extracts,against the Kunming mice.In acute study,we firstly tested median lethal dose(LD50)in mice of three cadinene sesquiterpenes 2-deoxo-2-(acetyloxy)-9-oxoageraphorone(DAOA),9-oxo-agerophorone(OA)and 9-oxo-10,11-dehydro-agerophorone(ODA)from Eupatorium adenophorum(Ea).DAOA(215–4640 mg/kg BW,given orally)showed lowest LD50 at 926 mg/kg BW for male mice in contrast with OA(1470 mg/kg BW)and ODA(1470 mg/kg BW).In sub-acute study,repeated doses(75–300 mg/kg BW,for 7 days)of DAOA/OA increased blood parameters,liver and spleen index in dose dependent relationship,along with decrease in thymus index.The blood biochemical and histopathological examination showed that DAOA/OA dose 300 mg/kg BW significantly causes pathological changes of hepatic lobules and hepatocytes,which are consistent with cholestasis and hepatic injury.75 mg/kg dose of DAOA/OA was found to be approximately/totally safe over the span of 7 days treatment showing no change in all above described parameters.Cadinene sesquiterpenes guarantee low risk to environment as a type of low toxic botanical components,which may find potential application in biopesticides development field.
