In this study,three new germacranolide sesquiterpenes(1–3),together with six related known analogues(4–9)were isolated from the whole plant of Carpesium cernuum.Their structures were established by a combination of ...In this study,three new germacranolide sesquiterpenes(1–3),together with six related known analogues(4–9)were isolated from the whole plant of Carpesium cernuum.Their structures were established by a combination of extensive NMR spectroscopic analysis,HR-ESIMS data,and ECD calculations.The anti-leukemia activities of all compounds towards three cell lines(HEL,KG-1a,and K562)were evaluated in vitro.Compounds 1–3 exhibited moderate cytotoxicity with IC50 values ranging from 1.59 to 5.47μmol·L^(−1).Mechanistic studies indicated that 2 induced apoptosis by decreasing anti-apoptotic protein Bcl-2 and activating the caspase family in K562 cells.These results suggest that compound 2 is a potential anti-leukemia agent.展开更多
A series of novel tetrahydro-4H-pyrano[3,2-c]pyridines（3a-3p） were synthesized and found to possess potent antiproliferative activity against leukemia K562 cells in vitro. Preliminary bioassay indicates that compoun...A series of novel tetrahydro-4H-pyrano[3,2-c]pyridines（3a-3p） were synthesized and found to possess potent antiproliferative activity against leukemia K562 cells in vitro. Preliminary bioassay indicates that compounds 3a and 3e afford the best activity, the IC50 values of them were 6.93 and 7.51μg/mL, respectively, which were lower than that of the anticancer drug 5-FU（1C50=8.56μg/mL）. To reduce the toxicity of compounds 3a-3p to the prolife- ration of normal bematopoietic cells, a tumor targeted CD14 monoclonal antibody（McAb） was used in conjugation with compounds 3a--3p to get conjugates 4a--4p, respectively. The inhibitory activities of conjugates 4a--4p toward K562 cells were discovered to approach those of compounds 3a--3p. In the presence of CD14 McAb, tumor cells were found to be much more susceptible to conjugates 3a--3p than normal hematopoietic cells. Therefore, the toxicity of conjugates 4a--4p to normal hematopoietic cells declined obviously. For example, as for the toxicity of compound 3a compared with that of compound 4a, the value of ICs0 increased from 35.90 μmol/L to 39.52 μmol/L.展开更多
优势骨架天然产物衍生物库的多样性合成是药物化学领域的重要研究方向。基于新的合成策略,以不同取代基的色原酮-氧化吲哚底物(1)和郁金香素A发生Michael加成反应,合成了7个未见文献报道的郁金香素A-氧化吲哚-色酮拼接化合物(3a~3g),产...优势骨架天然产物衍生物库的多样性合成是药物化学领域的重要研究方向。基于新的合成策略,以不同取代基的色原酮-氧化吲哚底物(1)和郁金香素A发生Michael加成反应,合成了7个未见文献报道的郁金香素A-氧化吲哚-色酮拼接化合物(3a~3g),产率75%~80%,dr>20∶1。化合物3的结构经1 H NMR,13 C NMR和HR-MS(ESI-TOF)表征,化合物3g的相对构型通过单晶X-射线衍射进行了确定。采用MTT法研究了化合物3对人白血病K562细胞的体外抗肿瘤活性。结果表明:化合物3b,3e和3f对人白血病K562细胞具有一定的抑制活性。展开更多
基金supported by the Science and Technology Department of Guizhou Province(No.QKHJC[2016]1002,81872772,81960546,and U1812403)the National Natural Science Foundation of China(Nos.81872772,81960546,and U1812403)+1 种基金the Science and Technology Department of Anshun City(No.ASKP[2019]3)the 100 Leading Talents of Guizhou Province(fund for LI Yan-Mei,Nos.P2018-KF11 and QZYY-019-022).
文摘In this study,three new germacranolide sesquiterpenes(1–3),together with six related known analogues(4–9)were isolated from the whole plant of Carpesium cernuum.Their structures were established by a combination of extensive NMR spectroscopic analysis,HR-ESIMS data,and ECD calculations.The anti-leukemia activities of all compounds towards three cell lines(HEL,KG-1a,and K562)were evaluated in vitro.Compounds 1–3 exhibited moderate cytotoxicity with IC50 values ranging from 1.59 to 5.47μmol·L^(−1).Mechanistic studies indicated that 2 induced apoptosis by decreasing anti-apoptotic protein Bcl-2 and activating the caspase family in K562 cells.These results suggest that compound 2 is a potential anti-leukemia agent.
基金the ＂Twelfth Five-Year＂ National Science and Technology Support Program，the National Natural Science Foundation of China，the Innovation Project of Shanghai Education Commission,China，the Leading Academic Discipline Project of Shanghai Normal University,China
文摘A series of novel tetrahydro-4H-pyrano[3,2-c]pyridines（3a-3p） were synthesized and found to possess potent antiproliferative activity against leukemia K562 cells in vitro. Preliminary bioassay indicates that compounds 3a and 3e afford the best activity, the IC50 values of them were 6.93 and 7.51μg/mL, respectively, which were lower than that of the anticancer drug 5-FU（1C50=8.56μg/mL）. To reduce the toxicity of compounds 3a-3p to the prolife- ration of normal bematopoietic cells, a tumor targeted CD14 monoclonal antibody（McAb） was used in conjugation with compounds 3a--3p to get conjugates 4a--4p, respectively. The inhibitory activities of conjugates 4a--4p toward K562 cells were discovered to approach those of compounds 3a--3p. In the presence of CD14 McAb, tumor cells were found to be much more susceptible to conjugates 3a--3p than normal hematopoietic cells. Therefore, the toxicity of conjugates 4a--4p to normal hematopoietic cells declined obviously. For example, as for the toxicity of compound 3a compared with that of compound 4a, the value of ICs0 increased from 35.90 μmol/L to 39.52 μmol/L.
文摘优势骨架天然产物衍生物库的多样性合成是药物化学领域的重要研究方向。基于新的合成策略,以不同取代基的色原酮-氧化吲哚底物(1)和郁金香素A发生Michael加成反应,合成了7个未见文献报道的郁金香素A-氧化吲哚-色酮拼接化合物(3a~3g),产率75%~80%,dr>20∶1。化合物3的结构经1 H NMR,13 C NMR和HR-MS(ESI-TOF)表征,化合物3g的相对构型通过单晶X-射线衍射进行了确定。采用MTT法研究了化合物3对人白血病K562细胞的体外抗肿瘤活性。结果表明:化合物3b,3e和3f对人白血病K562细胞具有一定的抑制活性。
