Tamoxifen resistance(TamR)is the underlying cause of treatment failure in many breast cancer patients receiving tamoxifen.In order to look for noncytotoxic natural products with the ability to reverse TamR,an extract ...Tamoxifen resistance(TamR)is the underlying cause of treatment failure in many breast cancer patients receiving tamoxifen.In order to look for noncytotoxic natural products with the ability to reverse TamR,an extract from strain Streptomyces sp.KIB-H0495 was detected to be active.Subsequent large scale fermentation and isolation led to the isolation of four a-pyrone derivatives including two new compounds,violapyrones J(2)and K(3),and two known analogues,violapyrones B(1)and I(4).Further bioactivity assays indicated that only 1 and 3 exerted potent resensitization effects on MCF-7/TamR cells at a concentration of 1 lM.Owing to the simple structures of 1 and 3,these two compounds might have potential for further investigation as novel tamoxifen resensitization agent in breast cancer chemotherapy.展开更多
Erythroxylum P.Browne is the largest and most representative genus of Erythroxylaceae family.It contains approxi-mately 230 species that are mainly distributed in tropical and subtropical regions.Some species in this ...Erythroxylum P.Browne is the largest and most representative genus of Erythroxylaceae family.It contains approxi-mately 230 species that are mainly distributed in tropical and subtropical regions.Some species in this genus,such as E.monogynum and E.coca,have been used as folk medicines in India or South America for a long history.It is well known that Erythroxylum plants are rich in tropane alkaloids,and the representative member cocaine shows remarka-ble activity in human central nervous system.However,many other types of active compounds have also been found in Erythroxylum along with the broadening and deepening of phytochemical research.To date,a total of 383 com-pounds from Erythroxylum have been reported,among which only 186 tropane alkaloids have been reviewed in 2010.In this review,we summarized all remained 197 compounds characterized from 53 Erythroxylum species from 1960 to 2021,which include diterpenes,triterpenes,alkaloids,flavonoids,and other derivates,providing a comprehensive overview of phytoconstituents profile of Erythroxylum plants.In addition,the biological activities of representative phytochemicals and crude extracts were also highlighted.展开更多
Camptothecin is a complex monoterpenoid indole alkaloid with remarkable antitumor activity.Given that two C-10 modified camptothecin derivatives,topotecan and irinotecan,have been approved as potent anticancer agents,...Camptothecin is a complex monoterpenoid indole alkaloid with remarkable antitumor activity.Given that two C-10 modified camptothecin derivatives,topotecan and irinotecan,have been approved as potent anticancer agents,there is a critical need for methods to access other aromatic ringfunctionalized congeners(e.g.,C-9,C-10,etc.).However,contemporary methods for chemical oxidation are generally harsh and low-yielding when applied to the camptothecin scaffold,thereby limiting the development of modified derivatives.Reported herein,we have identified four tailoring enzymes responsible for C-9 modifications of camptothecin from Nothapodytes tomentosa,via metabolomic and transcriptomic analysis.These consist of a cytochrome P450(Nt CPT9H)which catalyzes the regioselective oxidation of camptothecin to 9-hydroxycamptothecin,as well as two methyltransferases(Nt OMT1/2,converting 9-hydroxycamptothecin to 9-methoxycamptothecin),and a uridine diphosphate-glycosyltransferase(Nt UGT5,decorating 9-hydroxycamptothecin to9-β-D-glucosyloxycamptothecin).Importantly,the critical residues that contribute to the specific catalytic activity of Nt CPT9H have been elucidated through molecular docking and mutagenesis experiments.This work provides a genetic basis for producing camptothecin derivatives through metabolic engineering.This will hasten the discovery of novel C-9 modified camptothecin derivatives,with profound implications for pharmaceutical manufacture.展开更多
Two new myrinsol diterpenoids, euphordracunculins A(1) and B(2), together with three known analogues, euphorprolitherin B(3), proliferins A(4) and B(5),were isolated from the petroleum ether extract of the a...Two new myrinsol diterpenoids, euphordracunculins A(1) and B(2), together with three known analogues, euphorprolitherin B(3), proliferins A(4) and B(5),were isolated from the petroleum ether extract of the aerial parts of Euphorbia dracunculoides Lam. Their structures were elucidated by means of extensive spectroscopic analysis(NMR and ESI-MS) and comparison with data reported in the literature.展开更多
基金the National Natural Science Foundation of China to S-X.H(No.81522044)and to X.W(No.31471226)High-end Science and Technology Talents Program of Yunnan Province to S-X.H(No.2013HA022)a Grant from the Thousand Youth Talents Program of China.
文摘Tamoxifen resistance(TamR)is the underlying cause of treatment failure in many breast cancer patients receiving tamoxifen.In order to look for noncytotoxic natural products with the ability to reverse TamR,an extract from strain Streptomyces sp.KIB-H0495 was detected to be active.Subsequent large scale fermentation and isolation led to the isolation of four a-pyrone derivatives including two new compounds,violapyrones J(2)and K(3),and two known analogues,violapyrones B(1)and I(4).Further bioactivity assays indicated that only 1 and 3 exerted potent resensitization effects on MCF-7/TamR cells at a concentration of 1 lM.Owing to the simple structures of 1 and 3,these two compounds might have potential for further investigation as novel tamoxifen resensitization agent in breast cancer chemotherapy.
基金supported by the National Key R&D Program of China(2018YFA0900600)the National Science Foundation of China(U1902212 and 32000239)+2 种基金the Foundations of Yunnan Province(2019FJ007 and 2019ZF011-2)the Strategic Priority Research Program of the CAS(XDB27020205)the Key Research Program of Frontier Sciences of the CAS(QYZDB-SSW-SMC051).
文摘Erythroxylum P.Browne is the largest and most representative genus of Erythroxylaceae family.It contains approxi-mately 230 species that are mainly distributed in tropical and subtropical regions.Some species in this genus,such as E.monogynum and E.coca,have been used as folk medicines in India or South America for a long history.It is well known that Erythroxylum plants are rich in tropane alkaloids,and the representative member cocaine shows remarka-ble activity in human central nervous system.However,many other types of active compounds have also been found in Erythroxylum along with the broadening and deepening of phytochemical research.To date,a total of 383 com-pounds from Erythroxylum have been reported,among which only 186 tropane alkaloids have been reviewed in 2010.In this review,we summarized all remained 197 compounds characterized from 53 Erythroxylum species from 1960 to 2021,which include diterpenes,triterpenes,alkaloids,flavonoids,and other derivates,providing a comprehensive overview of phytoconstituents profile of Erythroxylum plants.In addition,the biological activities of representative phytochemicals and crude extracts were also highlighted.
基金supported by National Natural Science Foundation of China(82225043)Biological Resources Program(KFJBRP-009)+1 种基金Yunnan Revitalization Talent Support Program“Yunling Scholar”Project(S.-X.H.)Yunnan Revitalization Talent Support Program“Young Talent”Project(J.-P.H.)。
文摘Camptothecin is a complex monoterpenoid indole alkaloid with remarkable antitumor activity.Given that two C-10 modified camptothecin derivatives,topotecan and irinotecan,have been approved as potent anticancer agents,there is a critical need for methods to access other aromatic ringfunctionalized congeners(e.g.,C-9,C-10,etc.).However,contemporary methods for chemical oxidation are generally harsh and low-yielding when applied to the camptothecin scaffold,thereby limiting the development of modified derivatives.Reported herein,we have identified four tailoring enzymes responsible for C-9 modifications of camptothecin from Nothapodytes tomentosa,via metabolomic and transcriptomic analysis.These consist of a cytochrome P450(Nt CPT9H)which catalyzes the regioselective oxidation of camptothecin to 9-hydroxycamptothecin,as well as two methyltransferases(Nt OMT1/2,converting 9-hydroxycamptothecin to 9-methoxycamptothecin),and a uridine diphosphate-glycosyltransferase(Nt UGT5,decorating 9-hydroxycamptothecin to9-β-D-glucosyloxycamptothecin).Importantly,the critical residues that contribute to the specific catalytic activity of Nt CPT9H have been elucidated through molecular docking and mutagenesis experiments.This work provides a genetic basis for producing camptothecin derivatives through metabolic engineering.This will hasten the discovery of novel C-9 modified camptothecin derivatives,with profound implications for pharmaceutical manufacture.
基金financially supported by the National Natural Science Foundation of China(No.21162044)the Mid-aged and Young Academic and Technical Leader Raising Foundation of Yunnan Province(No.2010C1040)
文摘Two new myrinsol diterpenoids, euphordracunculins A(1) and B(2), together with three known analogues, euphorprolitherin B(3), proliferins A(4) and B(5),were isolated from the petroleum ether extract of the aerial parts of Euphorbia dracunculoides Lam. Their structures were elucidated by means of extensive spectroscopic analysis(NMR and ESI-MS) and comparison with data reported in the literature.