Bioassay-guided fractionation of an ethanolic extract of Ochrosia borbonica led to the isolation of two known pyridocarbazole alkaloids,ellipticine(1)and 9-methoxyellipticine(2),and six known monoterpenoid indole alka...Bioassay-guided fractionation of an ethanolic extract of Ochrosia borbonica led to the isolation of two known pyridocarbazole alkaloids,ellipticine(1)and 9-methoxyellipticine(2),and six known monoterpenoid indole alkaloids(3-8).Lipid-lowering assay in 3 T3-L1 cell model revealed that 1 and 2 could significantly inhibit the lipid droplet formation(EC50(28)0.41 and 0.92μmol·L^–1,respectively)and lower triglyceride levels by 50%-60%at the concentration of 1μmol·L^–1,being more potent than the positive drug luteolin(EC50(28)2.63μmol·L–^1).A mechanistic study indicated that 1 and 2 could intercalate into supercoiled DNA,which consequently inhibited the mitotic clonal expansion of 3 T3-L1 cells at the early differentiation phase,leading to the retardance of following adipogenesis and lipogenesis.These findings suggest that 1 and 2 may serve as promising leads for further d evelopment of anti-obesity drugs.展开更多
G-quadruplexes comprise a class of secondary structures that are formed in guanine-rich sequences in eukaryotic genomes and play a crucial role in the regulation of many biological events.G-quadruplexes have become ta...G-quadruplexes comprise a class of secondary structures that are formed in guanine-rich sequences in eukaryotic genomes and play a crucial role in the regulation of many biological events.G-quadruplexes have become targets for anticancer drugs with high selectivity vs.duplex DNA and low cytotoxicity against normal cells.Natural products and their derivatives display polymorphism,structural complexity,and potent activity.It is,therefore,reasonable to seek ligands targeting G-quadruplexes from natural products.Recently,many successful examples have been reported,showing ligands with excellent anticancer activities.In this review,we summarized the development of research on natural products and derivatives that target G-quadruplex structures in an effort to guide future studies.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81573302,81722042,and 81703336)the Guangdong Natural Science Funds for Distinguished Young Scholar(No.2014A0303 06047)+2 种基金the Science and Technology Planning Project of Guangdong Province,China(No.2015A020211007)the Fundamental Research Funds for the Central Universities(No.17ykzd12)the Guangdong Provincial Key Laboratory of Construction Foundation(No.2017B030314030)
文摘Bioassay-guided fractionation of an ethanolic extract of Ochrosia borbonica led to the isolation of two known pyridocarbazole alkaloids,ellipticine(1)and 9-methoxyellipticine(2),and six known monoterpenoid indole alkaloids(3-8).Lipid-lowering assay in 3 T3-L1 cell model revealed that 1 and 2 could significantly inhibit the lipid droplet formation(EC50(28)0.41 and 0.92μmol·L^–1,respectively)and lower triglyceride levels by 50%-60%at the concentration of 1μmol·L^–1,being more potent than the positive drug luteolin(EC50(28)2.63μmol·L–^1).A mechanistic study indicated that 1 and 2 could intercalate into supercoiled DNA,which consequently inhibited the mitotic clonal expansion of 3 T3-L1 cells at the early differentiation phase,leading to the retardance of following adipogenesis and lipogenesis.These findings suggest that 1 and 2 may serve as promising leads for further d evelopment of anti-obesity drugs.
基金supported by the National Natural Science Foundation of China(21172272,21272291)
文摘G-quadruplexes comprise a class of secondary structures that are formed in guanine-rich sequences in eukaryotic genomes and play a crucial role in the regulation of many biological events.G-quadruplexes have become targets for anticancer drugs with high selectivity vs.duplex DNA and low cytotoxicity against normal cells.Natural products and their derivatives display polymorphism,structural complexity,and potent activity.It is,therefore,reasonable to seek ligands targeting G-quadruplexes from natural products.Recently,many successful examples have been reported,showing ligands with excellent anticancer activities.In this review,we summarized the development of research on natural products and derivatives that target G-quadruplex structures in an effort to guide future studies.
