未经批准:人参具有抗肿瘤作用,人参皂苷被认为是其主要活性化学成分之一。人参皂苷可以进一步水解生成次级皂苷,20(R)-泛三醇是人参皂苷的重要皂甙元。我们旨在从20(R)-人参三醇合成一种新的人参皂甙衍生物,并研究其体内和体外抗肿瘤活性。
未经评估:这里,选择20(R)-帕索三醇作为前体并修饰为其衍生物。新产品经1H-NMR表征,13C-NMR和HR-MS,并通过分子对接评估,MTT,荧光素酶报告分析,西方印迹,免疫荧光染色,集落形成试验,EdU标记和免疫荧光,凋亡测定,细胞迁移试验,transwell测定和体内抗肿瘤活性测定。
UNASSIGNED:具有最佳抗肿瘤活性的衍生物被鉴定为6,12-二羟基-4,4,8,10,14-五甲基-17-(2,6,6-三甲基四氢-2H-吡喃-2-基)十六烷基-1H-环[a]菲酚-3-基(叔丁氧羰基)甘氨酸酯(A11)。本研究的重点是衍生物的抗肿瘤活性。衍生物A11(IC50<0.3μM)的效力比20(R)-泛他三醇(IC50>30μM)的效力高100倍以上。此外,A11以剂量依赖的方式抑制缺氧条件下HeLa细胞中缺氧诱导因子HIF-1α的蛋白表达和核积累。此外,A11剂量依赖性地抑制增殖,迁移,以及HeLa细胞的入侵,同时促进其凋亡。值得注意的是,在体内,A11的抑制作用比20(R)-帕索三醇的抑制作用更为显着(p<0.01)。
未经授权:据我们所知,这是首次报道从20(R)-panaxtriol生产衍生物A11及其与其前体相比具有优异的抗肿瘤活性的研究。此外,衍生物A11可用于进一步研究和开发新型抗肿瘤药物。
UNASSIGNED: Ginseng possesses antitumor effects, and ginsenosides are considered to be one of its main active chemical components. Ginsenosides can further be hydrolyzed to generate secondary saponins, and 20(R)-panaxotriol is an important sapogenin of ginsenosides. We aimed to synthesize a new ginsengenin derivative from 20(R)-panaxotriol and investigate its antitumor activity in vivo and in vitro.
UNASSIGNED: Here, 20(R)-panaxotriol was selected as a precursor and was modified into its derivatives. The new products were characterized by 1H-NMR, 13C-NMR and HR-MS and evaluated by molecular docking, MTT, luciferase reporter assay, western blotting, immunofluorescent staining, colony formation assay, EdU labeling and immunofluorescence, apoptosis assay, cells migration assay, transwell assay and in vivo antitumor activity assay.
UNASSIGNED: The derivative with the best antitumor activity was identified as 6,12-dihydroxy-4,4,8,10,14-pentamethyl-17-(2,6,6-trimethyltetrahydro-2H-pyran-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl(tert-butoxycarbonyl)glycinate (A11). The focus of this research was on the antitumor activity of the derivatives. The efficacy of the derivative A11 (IC50 < 0.3 μM) was more than 100 times higher than that of 20(R)- panaxotriol (IC50 > 30 μM). In addition, A11 inhibited the protein expression and nuclear accumulation of the hypoxia-inducible factor HIF-1α in HeLa cells under hypoxic conditions in a dose-dependent manner. Moreover, A11 dose-dependently inhibited the proliferation, migration, and invasion of HeLa cells, while promoting their apoptosis. Notably, the inhibition by A11 was more significant than that by 20(R)-panaxotriol (p < 0.01) in vivo.
UNASSIGNED: To our knowledge, this is the first study to report the production of derivative A11 from 20(R)-panaxotriol and its superior antitumor activity compared to its precursor. Moreover, derivative A11 can be used to further study and develop novel antitumor drugs.