94482-51-6Relevant articles and documents
Synthesis, anticancer evaluation and mechanism studies of novel indolequinone derivatives of ursolic acid
Wang, Wen-Yan,Wu, Wen-Yi,Li, A-Liang,Liu, Qing-Song,Sun, Yue,Gu, Wen
, (2021)
A series of novel indolequinone derivatives of ursolic acid bearing ester, hydrazide, or amide moieties were designed, synthesized, and screened for their in vitro antiproliferative activities against three cancer cell lines (MCF-7, HeLa, and HepG2) and a normal gastric mucosal cell line (Ges-1). A number of compounds showed significant activity against tested cancer cell lines. Among them, compound 6t exhibited the most potent activity against three cancer cell lines with IC50 values of 1.66 ± 0.21, 3.16 ± 0.24, and 10.35 ± 1.63 μM, respectively, and considerably lower cytotoxicity to Ges-1 cells. Especially, compound 6t could arrest cell cycle at S phase, suppress the migration of MCF-7 cells, elevate intracellular reactive oxygen species (ROS) level, and decrease mitochondrial membrane potential. Western blot analysis showed that compound 6t upregulated Bax, cleaved caspase-3/9, cleaved PARP levels and downregulated Bcl-2 level of MCF-7 cells. All these results indicated that compound 6t could significantly induce the apoptosis of MCF-7 cells. Meanwhile, compound 6t markedly decreased p-AKT and p-mTOR expression, which revealed that compound 6t probably exerted its cytotoxicity through targeting PI3K/AKT/mTOR signaling pathway. Therefore, compound 6t could be a promising lead for the discovery of novel anticancer agents.
Design, synthesis, anticancer activity and mechanism studies of novel 2-amino-4-aryl-pyrimidine derivatives of ursolic acid
Gu, Wen,Li, A-Liang,Liu, Qing-Song,Sun, Yue,Wang, Wen-Yan,Yang, Zi-Hui
, p. 2335 - 2350 (2022/02/16)
A series of novel 2-amino-4-aryl-pyrimidine derivatives of ursolic acid were designed, synthesized, and evaluated for their anticancer activities against four cancer cell lines (MCF-7, HeLa, HepG2, and A549) and a human hepatocyte cell line (LO2) via MTT assay. Among these derivatives, compound 7b exhibited potent cytotoxic activity against MCF-7 and HeLa cells with IC50 values of 0.48 ± 0.11 and 0.74 ± 0.13 μM, respectively, and substantially lower cytotoxicity to LO2 cells. Further cellular mechanism studies in MCF-7 cells elucidated that compound 7b could inhibit cell migration, induce cell cycle arrest at S phase and trigger mitochondrial-related apoptosis by increasing the generation of intracellular ROS and decreasing the mitochondrial membrane potential (MMP), which was associated with upregulation of the protein expression level of Bax and downregulation the level of Bcl-2 and the activation of caspase cascade. Western blot analyses also revealed that compound 7b could simultaneously suppress RAS/Raf/MEK/ERK and PI3K/AKT/mTOR signaling pathways, which could be responsible for the induction of apoptosis. Molecular docking study revealed that MEK1 kinase could be one of the possible targets of the title compounds. These results offered a promising scaffold for the investigation of novel targeted anticancer agents.
Synthesis and biological evaluation of pentacyclic triterpenoid derivatives as potential novel antibacterial agents
Wu, Panpan,Tu, Borong,Liang, Jinfeng,Guo, Shengzhu,Cao, Nana,Chen, Silin,Luo, Zhujun,Li, Jiahao,Zheng, Wende,Tang, Xiaowen,Li, Dongli,Xu, Xuetao,Liu, Wenfeng,Zheng, Xi,Sheng, Zhaojun,Roberts, Adam P.,Zhang, Kun,Hong, Weiqian David
, (2021/02/26)
A series of ursolic acid (UA), oleanolic acid (OA) and 18β-glycyrrhetinic acid (GA) derivatives were synthesized by introducing a range of substituted aromatic side-chains at the C-2 position after the hydroxyl group at C-3 position was oxidized. Their antibacterial activities were evaluated in vitro against a panel of four Staphylococcus spp. The results revealed that the introduction of aromatic side-chains at the C-2 position of GA led to the discovery of potent triterpenoid derivatives for inhibition of both drug sensitive and resistant S. aureus, while the other two series derivatives of UA and OA showed no significant antibacterial activity even at high concentrations. In particular, GA derivative 33 showed good potency against all four Staphylococcus spp. (MIC = 1.25–5 μmol/L) with acceptable pharmacokinetics properties and low cytotoxicity in vitro. Molecular docking was also performed using S. aureus DNA gyrase to rationalize the observed antibacterial activity. This series of GA derivatives has strong potential for the development of a new type of triterpenoid antibacterial agent.
