Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells.In this manuscript,guided by cascaded one strain many compounds-global natural products socia...Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells.In this manuscript,guided by cascaded one strain many compounds-global natural products social molecular networking(OSMAC-GNPS)strategy,a pair of epimeric environmental-induced metabolites were isolated from Aspergillus sp.EGF 15-0-3.Structurally,sterpiperazines A(1)and B(2)represent the first steroid-based indole alkaloids with unprecedented backbones.Biologically,compound 1 could be identified as a novel tyrosyl-DNA phosphodiesterase 1(Tdp1)inhibitor with a unique mechanism distinct from the reported modulators,and was able to significantly enhance the sensitivity of NCI-H460 cells to the clinic chemotherapeutic drug through inhibiting the DNA repairment and enhanced the DNA damage of cancer cells.展开更多
Callisalignenes G–I(1–3),three new meroterpenoids of b-triketone and monoterpene,along with two known analogues(4 and 5),were isolated from Callistemon salignus.Their structures and absolute configurations were unam...Callisalignenes G–I(1–3),three new meroterpenoids of b-triketone and monoterpene,along with two known analogues(4 and 5),were isolated from Callistemon salignus.Their structures and absolute configurations were unambiguously established by a combination of NMR and MS analysis and electronic circular dichroism(ECD)evidence.Callisalignenes H(2)and I(3)have a rare sec-butyl moiety at C-7.Meroterpenoids 1–3 exhibited cytotoxicity against HCT116 cells with IC50 values of 8.51±1.8,9.12±0.3,and 16.33±3.3 lM,respectively.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82273845,82304331,and 82360695)Guangxi Natural Science Foundation project(No.2023GXNSFBA026305).
文摘Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells.In this manuscript,guided by cascaded one strain many compounds-global natural products social molecular networking(OSMAC-GNPS)strategy,a pair of epimeric environmental-induced metabolites were isolated from Aspergillus sp.EGF 15-0-3.Structurally,sterpiperazines A(1)and B(2)represent the first steroid-based indole alkaloids with unprecedented backbones.Biologically,compound 1 could be identified as a novel tyrosyl-DNA phosphodiesterase 1(Tdp1)inhibitor with a unique mechanism distinct from the reported modulators,and was able to significantly enhance the sensitivity of NCI-H460 cells to the clinic chemotherapeutic drug through inhibiting the DNA repairment and enhanced the DNA damage of cancer cells.
基金National Natural Science Foundation of China(Nos.31600283 and 31570363)fund of State Key Laboratory of Phytochemistry and Plant Resources in West China(No.P2017-ZZ04)from Kunming Institute of Botany,Chinese Academy of Sciences.
文摘Callisalignenes G–I(1–3),three new meroterpenoids of b-triketone and monoterpene,along with two known analogues(4 and 5),were isolated from Callistemon salignus.Their structures and absolute configurations were unambiguously established by a combination of NMR and MS analysis and electronic circular dichroism(ECD)evidence.Callisalignenes H(2)and I(3)have a rare sec-butyl moiety at C-7.Meroterpenoids 1–3 exhibited cytotoxicity against HCT116 cells with IC50 values of 8.51±1.8,9.12±0.3,and 16.33±3.3 lM,respectively.
