The presence of anticancer clerodane diterpenoids is a chemotaxonomic marker for the traditional Chinese medicinal plant Scutellaria barbata,although the molecular mechanisms behind clerodane biosynthesis are unknown....The presence of anticancer clerodane diterpenoids is a chemotaxonomic marker for the traditional Chinese medicinal plant Scutellaria barbata,although the molecular mechanisms behind clerodane biosynthesis are unknown.Here,we report a high-quality assembly of the 414.98 Mb genome of S.barbata into 13 pseudochromosomes.Using phylogenomic and biochemical data,we mapped the plastidial metabolism of kaurene(gibberellins),abietane,and clerodane diterpenes in three species of the family Lamiaceae(Scutellaria barbata,Scutellaria baicalensis,and Salvia splendens),facilitating the identification of genes involved in the biosynthesis of the clerodanes,kolavenol,and isokolavenol.We show that clerodane biosynthesis evolved through recruitment and neofunctionalization of genes from gibberellin and abietane metabolism.Despite the assumed monophyletic origin of clerodane biosynthesis,which is widespread in species of the Lamiaceae,our data show distinct evolutionary lineages and suggest polyphyletic origins of clerodane biosynthesis in the family Lamiaceae.Our study not only provides significant insights into the evolution of clerodane biosynthetic pathways in the mint family,Lamiaceae,but also will facilitate the production of anticancer clerodanes through future metabolic engineering efforts.展开更多
Phytochemical investigation of the leaves and twigs of Callicarpa cathayana led to the isolation of six new clerodane diterpenoids,cathayanalactones A-F(1-6),together with seven analogues(7-13).Their structures were e...Phytochemical investigation of the leaves and twigs of Callicarpa cathayana led to the isolation of six new clerodane diterpenoids,cathayanalactones A-F(1-6),together with seven analogues(7-13).Their structures were established by extensive NMR analyses together with experimental and calculated ECD spectra analyses.Compounds 1,2,3,7 and 11 showed inhibitory activities on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells.展开更多
Glandular trichomes produce a wide variety of secondary metabolites that are considered as major defensive chemicals against herbivore attack.The morphology and secondary metabolites of the peltate glandular trichomes...Glandular trichomes produce a wide variety of secondary metabolites that are considered as major defensive chemicals against herbivore attack.The morphology and secondary metabolites of the peltate glandular trichomes of a lianoid Labiatae,Colquhounia seguinii Vaniot,were investigated.Three new clerodane diterpenoids,seguiniilactones A-C（1-3）,were identified through precise trichome collection with laser microdissection,metabolic analysis with ultra performance liquid chromatography-tandem mass spectrometer,target compound isolation with classical phytochemical techniques,structure elucidation with spectroscopic methods.All compounds showed significant antifeedant activity against a generalist plant-feeding insect Spodoptera exigua.Seguiniilactone A（1） was approximately 17-fold more potent than the commercial neem oil.a-Substituted α,β-unsaturated γ-lactone functionality was found to be crucial for strong antifeedant activity of this class of compounds.Quantitative results indicated that the levels of these compounds in the peltate glandular trichomes and leaves were sufficiently high to deter the feeding by generalist insects.Moderate antifungal activity was observed for seguiniilactone C（3） against six predominant fungal species isolated from the diseased leaves of C seguinii,while seguiniilactones A and B were generally inactive.These findings suggested that seguiniilactones A-C might be specialized secondary metabolites in peltate glandular trichomes for the plant defense against insect herbivores and pathogens.展开更多
Eight novel clerodane diterpenoids(1-8)were isolated from the twigs of Casearia graveolens.Their structures were elucidated through comprehensive nuclear magnetic resonance(NMR),high-resolution electrospray ionization...Eight novel clerodane diterpenoids(1-8)were isolated from the twigs of Casearia graveolens.Their structures were elucidated through comprehensive nuclear magnetic resonance(NMR),high-resolution electrospray ionization mass spectrometry(HRESI-MS),and electronic circular dichroism(ECD)analyses.In addition to structural determination,surface plasmon resonance(SPR)assays were conducted to investigate molecular interactions,revealing that compound 8 exhibited high affinity for vascular endothelial growth factor receptor 2(VEGFR2),a key regulator of tumor angiogenesis.Subsequent in vivo experiments demonstrated that compound 8 effectively inhibited angiogenesis and displayed significant antitumor activity by suppressing tumor proliferation and metastasis in zebrafish xenograft models.These findings suggest that compound 8 holds promise as an anticancer lead compound targeting VEGFR-2 to obstruct tumor angiogenesis.展开更多
The phytochemical investigation of the leaves and twigs of Croton yunnanensis resulted in the isolation of eight new clerodane furanoditerpenoids,named croyunfuranoids A-H(1-8),along with three known analogs(9-11).The...The phytochemical investigation of the leaves and twigs of Croton yunnanensis resulted in the isolation of eight new clerodane furanoditerpenoids,named croyunfuranoids A-H(1-8),along with three known analogs(9-11).The structures of these compounds were elucidated using spectroscopic analyses,and their absolute configurations were determined through a combination of electronic circular dichroism(ECD)calculations and single-crystal X-ray diffraction.Notably,Croyunfuranoid D(4)is identified as a rare 18,19-dinor-clerodane diterpenoid.Additionally,the structure of a previously reported diterpenoid,crotonyunnan B,was revised.All isolated compounds were evaluated for their inhibitory activities on nitric oxide(NO)production in LPS-induced RAW 264.7 macrophages.Among them,compounds 5 and 6 demonstrated significant inhibitory effects,with IC_(50)values of 20.33±2.31 and 22.80±1.31μmol·L^(-1),respectively.展开更多
Two new nor-ent-halimane diterpenes and three previously unreported nor-clerodane diterpenes,designated callicain-tides A-E(1-5),were isolated from Callicarpa integerrima.Compounds 1 and 2 feature a distinctive 5/6-me...Two new nor-ent-halimane diterpenes and three previously unreported nor-clerodane diterpenes,designated callicain-tides A-E(1-5),were isolated from Callicarpa integerrima.Compounds 1 and 2 feature a distinctive 5/6-membered ring system,while compounds 3-5 are characterized by progressively truncated carbon skeletons,containing 18,17,and 16 carbons,respectively.In addition,four known compounds 6-9 were also identified.Their structures were elucidated using advanced spectroscopic tech-niques,including nuclear magnetic resonance(NMR),high-resolution electrospray ionization mass spectrometry(HR-ESI-MS),ultra-violet(UV),infrared radiation(IR),optical rotatory dispersion(ORD),DP4+analysis and electronic circular dichroism(ECD),sup-ported by quantum chemical calculations.Compounds 1-9 were evaluated for their anti-MRSA activity.Among them,compound 6 demonstrated significant anti-MRSA activity,with a minimum inhibitory concentration(MIC)of 16 μg·mL^(-1).展开更多
Phytochemical investigation of the aerial parts of Dodonaea viscosa led to the isolation of six new compounds including four isoprenylated flavonoids,dodovisones A-D(1-4),and two clerodane diterpenoids,dodovislactones...Phytochemical investigation of the aerial parts of Dodonaea viscosa led to the isolation of six new compounds including four isoprenylated flavonoids,dodovisones A-D(1-4),and two clerodane diterpenoids,dodovislactones A and B(5 and 6).Their structures were established by extensive spectroscopic analysis.展开更多
Two new neo-clerodane diterpenoids, 6,7-dibenzoyloxybarbatin C （1, named barbatin D） and 6-（2-acetoxy-3-methylbutanoloxy）-7-（2-carbonyl-3-methylbutanoyloxy） barbatin C （2, named barbatin E） were isolated from ...Two new neo-clerodane diterpenoids, 6,7-dibenzoyloxybarbatin C （1, named barbatin D） and 6-（2-acetoxy-3-methylbutanoloxy）-7-（2-carbonyl-3-methylbutanoyloxy） barbatin C （2, named barbatin E） were isolated from the whole plant of Scutellaria barbata D. Don. Their structures were elucidated by spectroscopic methods including extensive 1 D and 2D NMR analyses. In vitro, compounds 1-2 showed cytotoxic activities against three human cancer lines, namely, HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells, and with IC50 values in the range of 3.5-6.7μM.展开更多
Salvia dugesii is an invasive plant in Yunnan,China.To tentatively explore its utilization,a systematic phytochemical investigation was carried out on this plant,which led to the isolation of five new neo-clerodane di...Salvia dugesii is an invasive plant in Yunnan,China.To tentatively explore its utilization,a systematic phytochemical investigation was carried out on this plant,which led to the isolation of five new neo-clerodane diterpenoids,dugesins C-G(1-5),together with six known ones.Their structures were determined by comprehensive NMR and MS spectroscopic analysis.It was noteworthy that the eleven isolates,composed of five different carbocyclic systems derived from the neo-clerodane diterpenoid skeleton,were reported from the same plant for the first time.The anti-feedantial,cytotoxic,and antiviral activities of the isolates were evaluated.Dugesin F(4)was tested to be a non-toxic antiviral compound against influenza virus FM1.展开更多
基金the Royal Society for the Newton Advanced Fellowship awarded to E.C.T.(NAF\R2\192001)and CEPAMS Funding(Project CPM19)for support of the collaboration project‘‘Scutellaria Anticancer Metabolites’’for C.M.and E.C.T.C.M.was also supported by the Institute Strategic Programme‘‘Molecules from Nature’’(BB/P012523/1)from the UK Biotechnology and Biological Sciences Research Council.E.C.T.was also supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB27020204)International Partnership Program of Chinese Academy of Sciences(153D31KYSB 20160074)Ministry of Science and Technology for Foreign Expert Project 2019(G20190113016),the Science and Technology Commission of Shanghai Municipality for Shanghai Talent Recruitment Programs.A.L.M.M.was supported by the CAS PIFI Fellowship and the China Postdoctoral Science Foundation for Postdoctoral International Exchange Program Fellowship.H.L.is supported by the National Natural Science Foundation of China through Young Scientists Fund(32200313).
文摘The presence of anticancer clerodane diterpenoids is a chemotaxonomic marker for the traditional Chinese medicinal plant Scutellaria barbata,although the molecular mechanisms behind clerodane biosynthesis are unknown.Here,we report a high-quality assembly of the 414.98 Mb genome of S.barbata into 13 pseudochromosomes.Using phylogenomic and biochemical data,we mapped the plastidial metabolism of kaurene(gibberellins),abietane,and clerodane diterpenes in three species of the family Lamiaceae(Scutellaria barbata,Scutellaria baicalensis,and Salvia splendens),facilitating the identification of genes involved in the biosynthesis of the clerodanes,kolavenol,and isokolavenol.We show that clerodane biosynthesis evolved through recruitment and neofunctionalization of genes from gibberellin and abietane metabolism.Despite the assumed monophyletic origin of clerodane biosynthesis,which is widespread in species of the Lamiaceae,our data show distinct evolutionary lineages and suggest polyphyletic origins of clerodane biosynthesis in the family Lamiaceae.Our study not only provides significant insights into the evolution of clerodane biosynthetic pathways in the mint family,Lamiaceae,but also will facilitate the production of anticancer clerodanes through future metabolic engineering efforts.
基金supported by Yunnan Applicative and Basic Research Program(Nos.2018FY001 and 2018FA048)the National Natural Science Foundation of China(Nos.81422046,81860615 and 21762048)+4 种基金the Foundation of Yunnan Educational Committee(No.2018JS002)the Natural Science Foundation of Yunnan University(No.2017YDQN03)the Key Laboratory of Medicinal Chemistry for Natural Resource,Ministry of Education(No.2017KF02)the Program for Changjiang Scholars and Innovative Research Team in University(No.IRT_17R94)Project of Innovative Research Team of Yunnan Province to XIAO Wei-Lie
文摘Phytochemical investigation of the leaves and twigs of Callicarpa cathayana led to the isolation of six new clerodane diterpenoids,cathayanalactones A-F(1-6),together with seven analogues(7-13).Their structures were established by extensive NMR analyses together with experimental and calculated ECD spectra analyses.Compounds 1,2,3,7 and 11 showed inhibitory activities on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells.
基金supported financially by the NSFC-Yunnan Joint Fund(U1202263)the National Basic Research Program of China(973 Program) on Biological Control of Key Crop Pathogenic Nematodes(2013CB127505)+1 种基金the National Natural Science Foundation of China(31070320,31470395 and 31100222)the "Hundred Talents Program" of the Chinese Academy of Sciences(awarded to SH Li)
文摘Glandular trichomes produce a wide variety of secondary metabolites that are considered as major defensive chemicals against herbivore attack.The morphology and secondary metabolites of the peltate glandular trichomes of a lianoid Labiatae,Colquhounia seguinii Vaniot,were investigated.Three new clerodane diterpenoids,seguiniilactones A-C（1-3）,were identified through precise trichome collection with laser microdissection,metabolic analysis with ultra performance liquid chromatography-tandem mass spectrometer,target compound isolation with classical phytochemical techniques,structure elucidation with spectroscopic methods.All compounds showed significant antifeedant activity against a generalist plant-feeding insect Spodoptera exigua.Seguiniilactone A（1） was approximately 17-fold more potent than the commercial neem oil.a-Substituted α,β-unsaturated γ-lactone functionality was found to be crucial for strong antifeedant activity of this class of compounds.Quantitative results indicated that the levels of these compounds in the peltate glandular trichomes and leaves were sufficiently high to deter the feeding by generalist insects.Moderate antifungal activity was observed for seguiniilactone C（3） against six predominant fungal species isolated from the diseased leaves of C seguinii,while seguiniilactones A and B were generally inactive.These findings suggested that seguiniilactones A-C might be specialized secondary metabolites in peltate glandular trichomes for the plant defense against insect herbivores and pathogens.
基金supported by the National Natural Science Foundation of China(No.22077067)the Project of State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University[No.QJJ(2022)422]the 111 Project(No.B20016)。
文摘Eight novel clerodane diterpenoids(1-8)were isolated from the twigs of Casearia graveolens.Their structures were elucidated through comprehensive nuclear magnetic resonance(NMR),high-resolution electrospray ionization mass spectrometry(HRESI-MS),and electronic circular dichroism(ECD)analyses.In addition to structural determination,surface plasmon resonance(SPR)assays were conducted to investigate molecular interactions,revealing that compound 8 exhibited high affinity for vascular endothelial growth factor receptor 2(VEGFR2),a key regulator of tumor angiogenesis.Subsequent in vivo experiments demonstrated that compound 8 effectively inhibited angiogenesis and displayed significant antitumor activity by suppressing tumor proliferation and metastasis in zebrafish xenograft models.These findings suggest that compound 8 holds promise as an anticancer lead compound targeting VEGFR-2 to obstruct tumor angiogenesis.
基金supported by the National Natural Science Foundation of China(Nos.82104020 and 82130111)the High-level Innovative Research Institute of Department of Science and Technology of Guangdong Province(No.2021B0909050003)the High-level New R&D Institute of Department of Science and Technology of Guangdong Province(No.2019B090904008)。
文摘The phytochemical investigation of the leaves and twigs of Croton yunnanensis resulted in the isolation of eight new clerodane furanoditerpenoids,named croyunfuranoids A-H(1-8),along with three known analogs(9-11).The structures of these compounds were elucidated using spectroscopic analyses,and their absolute configurations were determined through a combination of electronic circular dichroism(ECD)calculations and single-crystal X-ray diffraction.Notably,Croyunfuranoid D(4)is identified as a rare 18,19-dinor-clerodane diterpenoid.Additionally,the structure of a previously reported diterpenoid,crotonyunnan B,was revised.All isolated compounds were evaluated for their inhibitory activities on nitric oxide(NO)production in LPS-induced RAW 264.7 macrophages.Among them,compounds 5 and 6 demonstrated significant inhibitory effects,with IC_(50)values of 20.33±2.31 and 22.80±1.31μmol·L^(-1),respectively.
基金supported by the National Natural Science Foundation of China(Nos.22477108,82260682)the Program for Changjiang Scholars and Innovative Research Team in University(No.IRT_17R94)+1 种基金the Project of Yunnan Characteristic Plant Screening and R&D Service CXO Platform(No.2022YKZY001)the Scientific Research Fund of Yunnan Provincial Department ofEducation(No.2023Y0235)。
文摘Two new nor-ent-halimane diterpenes and three previously unreported nor-clerodane diterpenes,designated callicain-tides A-E(1-5),were isolated from Callicarpa integerrima.Compounds 1 and 2 feature a distinctive 5/6-membered ring system,while compounds 3-5 are characterized by progressively truncated carbon skeletons,containing 18,17,and 16 carbons,respectively.In addition,four known compounds 6-9 were also identified.Their structures were elucidated using advanced spectroscopic tech-niques,including nuclear magnetic resonance(NMR),high-resolution electrospray ionization mass spectrometry(HR-ESI-MS),ultra-violet(UV),infrared radiation(IR),optical rotatory dispersion(ORD),DP4+analysis and electronic circular dichroism(ECD),sup-ported by quantum chemical calculations.Compounds 1-9 were evaluated for their anti-MRSA activity.Among them,compound 6 demonstrated significant anti-MRSA activity,with a minimum inhibitory concentration(MIC)of 16 μg·mL^(-1).
基金This work was financially supported by National Basic Research Program of China(973 Program,2009CB522300)the“West Light”program of Chinese Academy of Sciencesthe“Large-scale Compound Library”project of National Development Reform Commission.
文摘Phytochemical investigation of the aerial parts of Dodonaea viscosa led to the isolation of six new compounds including four isoprenylated flavonoids,dodovisones A-D(1-4),and two clerodane diterpenoids,dodovislactones A and B(5 and 6).Their structures were established by extensive spectroscopic analysis.
基金the National Natural Science Foundation of China (20772104).
文摘Two new neo-clerodane diterpenoids, 6,7-dibenzoyloxybarbatin C （1, named barbatin D） and 6-（2-acetoxy-3-methylbutanoloxy）-7-（2-carbonyl-3-methylbutanoyloxy） barbatin C （2, named barbatin E） were isolated from the whole plant of Scutellaria barbata D. Don. Their structures were elucidated by spectroscopic methods including extensive 1 D and 2D NMR analyses. In vitro, compounds 1-2 showed cytotoxic activities against three human cancer lines, namely, HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells, and with IC50 values in the range of 3.5-6.7μM.
基金This work was supported financially by the National Basic Research Program of China(2009CB522300)the National Natural Science Foundation of China(No.20702054)+2 种基金Shanghai Landscaping Administration Bureau Program(G102404)the foundation from the Chinese Academy of Sciences(2010KIBA10)the Young Academic and Technical Leader Raising Foundation of Yunnan Province(No.2009CI073).
文摘Salvia dugesii is an invasive plant in Yunnan,China.To tentatively explore its utilization,a systematic phytochemical investigation was carried out on this plant,which led to the isolation of five new neo-clerodane diterpenoids,dugesins C-G(1-5),together with six known ones.Their structures were determined by comprehensive NMR and MS spectroscopic analysis.It was noteworthy that the eleven isolates,composed of five different carbocyclic systems derived from the neo-clerodane diterpenoid skeleton,were reported from the same plant for the first time.The anti-feedantial,cytotoxic,and antiviral activities of the isolates were evaluated.Dugesin F(4)was tested to be a non-toxic antiviral compound against influenza virus FM1.
