Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)had caused a global pandemic since 2019,and posed a serious threat to global health security.Traditional Chinese medicin...Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)had caused a global pandemic since 2019,and posed a serious threat to global health security.Traditional Chinese medicine(TCM)has played an indispensable role in the battle against the epidemic.Many components originated from TCMs were found to inhibit the production of SARS-CoV-23C-like protease(3CLpro)and papain-like protease(PLpro),which are two promising therapeutic targets to inhibit SARS-CoV-2.This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis,which results in the characterization of 12 new flavonoids,including seven prenylated flavanones(1−7),one prenylated flavonol(8),two prenylated chalcones(9−10),one isoflavanone(11),and one isoflavan dimer(12),together with 43 known compounds(13−55).Their structures including the absolute configurations were elucidated by comprehensive analysis of MS,1D and 2D NMR data,and time-dependent density functional theory electronic circular dichroism(TDDFT ECD)calculations.Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-23CLpro with IC_(50) values of 34.89 and 19.88μmol·L^(−1),repectively while compounds 9,43 and 47 exhibited inhibitory effects against PLpro with IC_(50) values of 32.67,79.38,and 16.74μmol·L^(−1),respectively.展开更多
Multidrug resistance(MDR)mediated by ATP binding cassette subfamily B member 1(ABCB1)is significantly hindering effective cancer chemotherapy.However,currently,no ABCB1-inhibitory drugs have been approved to treat MDR...Multidrug resistance(MDR)mediated by ATP binding cassette subfamily B member 1(ABCB1)is significantly hindering effective cancer chemotherapy.However,currently,no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically,mainly due to the inhibitor specificity,toxicity,and drug interactions.Here,we reported that three polyoxypregnanes(POPs)as the most abundant constituents of Marsdenia tenacissima(M.tenacissima)were novel ABCB1-modulatory pro-drugs,which underwent intestinal microbiota-mediated biotransformation in vivo to generate active metabolites.The metabolites at non-toxic concentrations restored chemosensitivity in ABCB1-overexpressing cancer cells via inhibiting ABCB1 efflux activity without changing ABCB1 protein expression,which were further identified as specific non-competitive inhibitors of ABCB1 showing multiple binding sites within ABCB1 drug cavity.These POPs did not exhibit ABCB1/drug metabolizing enzymes interplay,and their repeated administration generated predictable pharmacokinetic interaction with paclitaxel without obvious toxicity in vivo.We further showed that these POPs enhanced the accumulation of paclitaxel in tumors and overcame ABCB1-mediated chemoresistance.The results suggested that these POPs had the potential to be developed as safe,potent,and specific pro-drugs to reverse ABCB1-mediated MDR.Our work also provided scientific evidence for the use of M.tenacissima in combinational chemotherapy.展开更多
Two new dimeric diterpenes, birhodomolleins D (1) and E (2), were characterized from the fruits of Rhododendron pumilum. Their structures featured two grayanane diterpenes dimerized through an oxygen bridge locati...Two new dimeric diterpenes, birhodomolleins D (1) and E (2), were characterized from the fruits of Rhododendron pumilum. Their structures featured two grayanane diterpenes dimerized through an oxygen bridge locating at C-3 and C-2'. They are the first examples of dimeric grayanane diterpenes with a 3-O-2' linkage from the Ericaceae family. Their structures were elucidated on the basis of comprehensive analysis of spectroscopic data.展开更多
A phytochemical investigation was carried out on the extract of a medicinal plant Callicarpa nudiflora,resulting in the characterization of five new 3,4-seco-isopimarane(1-5)and one new 3,4-seco-pimarane diterpenoid(6...A phytochemical investigation was carried out on the extract of a medicinal plant Callicarpa nudiflora,resulting in the characterization of five new 3,4-seco-isopimarane(1-5)and one new 3,4-seco-pimarane diterpenoid(6),together with four known compounds.The structures of the new compounds were fully elucidated by extensive analysis of MS,1 D and 2 D NMR spectroscopic data,and time-dependent density functional theory(TDDFT)calculation of electronic circular dichroism(ECD)spectra,and DFT calculations for NMR chemical shifts and optical rotations.展开更多
One new dimeric(1) and two monomeric sesquiterpene lactones(5 and 13), together with 10 known compounds(2-4, 6-12), were isolated from Artemisia heptapotamica collected in Almaty region of Kazakhstan. All compounds we...One new dimeric(1) and two monomeric sesquiterpene lactones(5 and 13), together with 10 known compounds(2-4, 6-12), were isolated from Artemisia heptapotamica collected in Almaty region of Kazakhstan. All compounds were isolated from this plant for the first time. The structures of the new compounds were mainly achieved by extensive analysis of MS, 1D and 2D NMR spectroscopic data, and ECD spectrum as well. The inhibitory activities of all isolates against activation of NF-κB induced by LPS were assessed on a THP1-Dual cell model. Some of them showed strong inhibitory activity with IC50 values ranging from 2 to 25μmol·L^-1.展开更多
Dicarabrols B and C(1 and 2),two new carabrane sesquiterpenoid dimers,along with one new carabrane sesquiterpenoid(3)were isolated from the whole plant of Carpesium abrotanoides L.Their full structures were establishe...Dicarabrols B and C(1 and 2),two new carabrane sesquiterpenoid dimers,along with one new carabrane sesquiterpenoid(3)were isolated from the whole plant of Carpesium abrotanoides L.Their full structures were established by extensive analysis of HR-ESI-MS and NMR spectroscopic data,and time-dependent density functional theory(TDDFT)electronic circular dichroism(ECD)calculations.Dicarabrol B possesses a novel C30 skeleton featuring a methylene-tethered bridge between two sesquiterpene moieties,while dicarabrol C presents the unique linkage of a cyclopentane ring in the molecule.Dicarabrol C exhibited potent inhibitory effects on HL−60 cells with an IC50 value of 3.7μmol·L^(−1).展开更多
Phytochemical investigation on the seeds of Caesalpinia sappan led to the isolation of five new cassanetype diterpenoids, named 11-oxo-phanginin A(1), caesalsappanins O–Q(2–4) and phanginin U(5),together with ...Phytochemical investigation on the seeds of Caesalpinia sappan led to the isolation of five new cassanetype diterpenoids, named 11-oxo-phanginin A(1), caesalsappanins O–Q(2–4) and phanginin U(5),together with five known compounds. The structures of the new compounds were elucidated by extensive analysis of mass spectrometric and 1D and 2D NMR spectroscopic data. All the new compounds showed moderate cytotoxic effects on human breast cancer MCF-7 and human colon cancer HCT116 cell lines.展开更多
Phytochemical investigation on the whole plant of Inula cappa led to the isolation of two new germacrane-type sesquiterpene lactones,ineupatolides D and E(1 and 2),together with three known analogs.The structures of...Phytochemical investigation on the whole plant of Inula cappa led to the isolation of two new germacrane-type sesquiterpene lactones,ineupatolides D and E(1 and 2),together with three known analogs.The structures of the new compounds were established by extensive analysis of 1Dand 2DNMR spectra,as well as MS data.Their absolute configurations were determined by CD spectra.All compounds showed moderate inhibitory effects on A431,A549,BGC-823,HL-60,HT-29,and MCF-7 cancer cell lines with IC50 values ranging from 2.1 to 36.3 μM.展开更多
A new semi-quinonechalcone C-glycoside isocartormin along with cartormin and saf fl omin C were isolated from the water extract of Carthamus tinctorius L. The structure of isocartormin was determined by extensive anal...A new semi-quinonechalcone C-glycoside isocartormin along with cartormin and saf fl omin C were isolated from the water extract of Carthamus tinctorius L. The structure of isocartormin was determined by extensive analysis of HR-MS, 1D-and 2D NMR data, and by comparison with those of cartormin reported previously by our group. Isocartormin was identified as a diastereoisomer of cartormin with a reverse configuration at C-18.展开更多
Birhodomolleins A-C(1-3),three novel diterpenoids dimerized from two grayanane diterpenes through an oxygen bridge,were isolated from the flowers of Rhododendron molle.Their structures were elucidated by interpretat...Birhodomolleins A-C(1-3),three novel diterpenoids dimerized from two grayanane diterpenes through an oxygen bridge,were isolated from the flowers of Rhododendron molle.Their structures were elucidated by interpretation of their 1D and 2D NMR and other spectroscopic data.Birhodomollein A(1) contains a rare chloro-substitution on one of the grayanane moieties.These are the first examples of dimeric diterpenes from the Ericaceae family.展开更多
基金This work was supported from the National Natural Science Foundation of China(Nos.82173696 and 21920102003)the Science and Technology Commission of Shanghai Municipality(Nos.20431900200 and 20430780300)+1 种基金the Strategic Priority Research Program of Chinese Academy of Sciences(Nos.SIMM010110 and SIMM040302)the Sustainable Development of Precious Traditional Chinese Medicine Resources(No.2060302-2001-01).
文摘Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)had caused a global pandemic since 2019,and posed a serious threat to global health security.Traditional Chinese medicine(TCM)has played an indispensable role in the battle against the epidemic.Many components originated from TCMs were found to inhibit the production of SARS-CoV-23C-like protease(3CLpro)and papain-like protease(PLpro),which are two promising therapeutic targets to inhibit SARS-CoV-2.This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis,which results in the characterization of 12 new flavonoids,including seven prenylated flavanones(1−7),one prenylated flavonol(8),two prenylated chalcones(9−10),one isoflavanone(11),and one isoflavan dimer(12),together with 43 known compounds(13−55).Their structures including the absolute configurations were elucidated by comprehensive analysis of MS,1D and 2D NMR data,and time-dependent density functional theory electronic circular dichroism(TDDFT ECD)calculations.Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-23CLpro with IC_(50) values of 34.89 and 19.88μmol·L^(−1),repectively while compounds 9,43 and 47 exhibited inhibitory effects against PLpro with IC_(50) values of 32.67,79.38,and 16.74μmol·L^(−1),respectively.
基金supported by Health and Medical Research Fund(HHSRF Project No.08090481,Hong Kong SAR,China)from Food and Health Bureau,HKSAROne-off Funding for Joint Lab/Research collaboration(Project code:3132968,Hong Kong SAR,China)from the Chinese University of Hong KongSeed Fund for Joint Establishments from School of Biomedical Science,the Chinese University of Hong Kong(China)
文摘Multidrug resistance(MDR)mediated by ATP binding cassette subfamily B member 1(ABCB1)is significantly hindering effective cancer chemotherapy.However,currently,no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically,mainly due to the inhibitor specificity,toxicity,and drug interactions.Here,we reported that three polyoxypregnanes(POPs)as the most abundant constituents of Marsdenia tenacissima(M.tenacissima)were novel ABCB1-modulatory pro-drugs,which underwent intestinal microbiota-mediated biotransformation in vivo to generate active metabolites.The metabolites at non-toxic concentrations restored chemosensitivity in ABCB1-overexpressing cancer cells via inhibiting ABCB1 efflux activity without changing ABCB1 protein expression,which were further identified as specific non-competitive inhibitors of ABCB1 showing multiple binding sites within ABCB1 drug cavity.These POPs did not exhibit ABCB1/drug metabolizing enzymes interplay,and their repeated administration generated predictable pharmacokinetic interaction with paclitaxel without obvious toxicity in vivo.We further showed that these POPs enhanced the accumulation of paclitaxel in tumors and overcame ABCB1-mediated chemoresistance.The results suggested that these POPs had the potential to be developed as safe,potent,and specific pro-drugs to reverse ABCB1-mediated MDR.Our work also provided scientific evidence for the use of M.tenacissima in combinational chemotherapy.
基金the financial support of the National Science & Technology Major Project“Key New Drug Creation and Manufacturing Program”(No.2015ZX09103002)the National Natural Science Fundation of China(No.81673327)the grants from the Key Laboratory of Drug Research, Shanghai Institute of Materia Medica(No. SIMM1501ZZ-03)
文摘Two new dimeric diterpenes, birhodomolleins D (1) and E (2), were characterized from the fruits of Rhododendron pumilum. Their structures featured two grayanane diterpenes dimerized through an oxygen bridge locating at C-3 and C-2'. They are the first examples of dimeric grayanane diterpenes with a 3-O-2' linkage from the Ericaceae family. Their structures were elucidated on the basis of comprehensive analysis of spectroscopic data.
基金supported from the China National Key R&D Program(Nos.2017YFE0195100 and 2018YFC.707000)the National Natural Science Foundation of China(Nos.21920102003 and 81903485)。
文摘A phytochemical investigation was carried out on the extract of a medicinal plant Callicarpa nudiflora,resulting in the characterization of five new 3,4-seco-isopimarane(1-5)and one new 3,4-seco-pimarane diterpenoid(6),together with four known compounds.The structures of the new compounds were fully elucidated by extensive analysis of MS,1 D and 2 D NMR spectroscopic data,and time-dependent density functional theory(TDDFT)calculation of electronic circular dichroism(ECD)spectra,and DFT calculations for NMR chemical shifts and optical rotations.
基金supported by the International Partnership Program of Chinese Academy of Sciences(No.153631KYSB20160004)the National Natural Science Foundation of China(Nos.81573305 and 81673327)the Ministry of Education and Science of the Republic of Kazakhstan(0118PK00458)
文摘One new dimeric(1) and two monomeric sesquiterpene lactones(5 and 13), together with 10 known compounds(2-4, 6-12), were isolated from Artemisia heptapotamica collected in Almaty region of Kazakhstan. All compounds were isolated from this plant for the first time. The structures of the new compounds were mainly achieved by extensive analysis of MS, 1D and 2D NMR spectroscopic data, and ECD spectrum as well. The inhibitory activities of all isolates against activation of NF-κB induced by LPS were assessed on a THP1-Dual cell model. Some of them showed strong inhibitory activity with IC50 values ranging from 2 to 25μmol·L^-1.
基金This work was supported by the China National Key R&D Program(Nos.2017YFE0195100 and 2018YFC1707000)the National Natural Science Foundation of China(Nos.21920102003 and 81903485).
文摘Dicarabrols B and C(1 and 2),two new carabrane sesquiterpenoid dimers,along with one new carabrane sesquiterpenoid(3)were isolated from the whole plant of Carpesium abrotanoides L.Their full structures were established by extensive analysis of HR-ESI-MS and NMR spectroscopic data,and time-dependent density functional theory(TDDFT)electronic circular dichroism(ECD)calculations.Dicarabrol B possesses a novel C30 skeleton featuring a methylene-tethered bridge between two sesquiterpene moieties,while dicarabrol C presents the unique linkage of a cyclopentane ring in the molecule.Dicarabrol C exhibited potent inhibitory effects on HL−60 cells with an IC50 value of 3.7μmol·L^(−1).
基金Financial support by Science and Technology Development Fund, Macao S.A.R (No. FDCT 120/2013/A3)the Research Fund of University of Macao (Nos. MYRG2014-00020-ICMS-QRCM and MYRG2015-00153-ICMS-QRCM)
文摘Phytochemical investigation on the seeds of Caesalpinia sappan led to the isolation of five new cassanetype diterpenoids, named 11-oxo-phanginin A(1), caesalsappanins O–Q(2–4) and phanginin U(5),together with five known compounds. The structures of the new compounds were elucidated by extensive analysis of mass spectrometric and 1D and 2D NMR spectroscopic data. All the new compounds showed moderate cytotoxic effects on human breast cancer MCF-7 and human colon cancer HCT116 cell lines.
基金Financial support from the National Science and Technology Major Project"Key New Drug Creation and Manufacturing Program"(Nos.2012ZX09301001-001,2015ZX09103002)the National Natural Science Funds of China(Nos.81302657,81573305,81473112)+3 种基金Youth Innovation Promotion Association CAS,the Ministry of Science and Technology(No.2010DFA30980)the Chinese Academy of Sciences(No.KSZD-EW-Z-004-01)the Shanghai Commission of Science and Technology(No.11DZ1970700,12JC1410300)the Research Fund of University of Macao(MYRG2014-00020-ICMS-QRCM and MYRG2015-00153ICMS-QRCM)
文摘Phytochemical investigation on the whole plant of Inula cappa led to the isolation of two new germacrane-type sesquiterpene lactones,ineupatolides D and E(1 and 2),together with three known analogs.The structures of the new compounds were established by extensive analysis of 1Dand 2DNMR spectra,as well as MS data.Their absolute configurations were determined by CD spectra.All compounds showed moderate inhibitory effects on A431,A549,BGC-823,HL-60,HT-29,and MCF-7 cancer cell lines with IC50 values ranging from 2.1 to 36.3 μM.
文摘A new semi-quinonechalcone C-glycoside isocartormin along with cartormin and saf fl omin C were isolated from the water extract of Carthamus tinctorius L. The structure of isocartormin was determined by extensive analysis of HR-MS, 1D-and 2D NMR data, and by comparison with those of cartormin reported previously by our group. Isocartormin was identified as a diastereoisomer of cartormin with a reverse configuration at C-18.
基金financial support of the National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"(Nos.2012ZX09301001-001,2015ZX09103002)the National Natural Science Fundation of China(Nos.81302657,81473112,81573305)
文摘Birhodomolleins A-C(1-3),three novel diterpenoids dimerized from two grayanane diterpenes through an oxygen bridge,were isolated from the flowers of Rhododendron molle.Their structures were elucidated by interpretation of their 1D and 2D NMR and other spectroscopic data.Birhodomollein A(1) contains a rare chloro-substitution on one of the grayanane moieties.These are the first examples of dimeric diterpenes from the Ericaceae family.