25576-27-6Relevant articles and documents
A-ring modified betulinic acid derivatives as potent cancer preventive agents
Hung, Hsin-Yi,Nakagawa-Goto, Kyoko,Tokuda, Harukuni,Iida, Akira,Suzuki, Nobutaka,Bori, Ibrahim D.,Qian, Keduo,Lee, Kuo-Hsiung
, p. 1005 - 1008 (2014)
Ten new 3,4-seco betulinic acid (BA) derivatives were designed and synthesized. Among them, compounds 7-15 exhibited enhanced chemopreventive ability in an in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation assay in Raji cells. Specifically, analogs with a free C-28 carboxylic acid, including 7, 8, 11, and 13, inhibited EBV-EA activation significantly. The most potent compound 8 displayed 100% inhibition at 1 × 103 mol ratio/TPA and 73.4%, 35.9%, and 8.4% inhibition at 5 × 102, 1 × 10 2, and 1 × 10 mol ratio/TPA, respectively, comparable with curcumin at high concentration and better than curcumin at low concentration. The potent chemopreventive activity of novel seco A-ring BAs (8 and 11) was further confirmed in an in vivo mouse skin carcinogenesis assay.
Identification and characterization of small molecule inhibitors of the ubiquitin ligases Siah1/2 in melanoma and prostate cancer cells
Feng, Yongmei,Sessions, E. Hampton,Zhang, Fan,Ban, Fuqiang,Placencio-Hickok, Veronica,Ma, Chen-Ting,Zeng, Fu-Yue,Pass, Ian,Terry, David B.,Cadwell, Gregory,Bankston, Laurie A.,Liddington, Robert C.,Chung, Thomas D.Y.,Pinkerton, Anthony B.,Sergienko, Eduard,Gleave, Martin,Bhowmick, Neil A.,Jackson, Michael R.,Cherkasov, Artem,Ronai, Ze'ev A.
, p. 145 - 162 (2019)
Inhibition of ubiquitin ligases with small molecule remains a very challenging task, given the lack of catalytic activity of the target and the requirement of disruption of its interactions with other proteins. Siah1/2, which are E3 ubiquitin ligases, are implicated in melanoma and prostate cancer and represent high-value drug targets. We utilized three independent screening approaches in our efforts to identify small-molecule Siah1/2 inhibitors: Affinity Selection-Mass Spectrometry, a protein thermal shift-based assay and an in silico based screen. Inhibitors were assessed for their effect on viability of melanoma and prostate cancer cultures, colony formation, prolyl-hydroxylase-HIF1α signaling, expression of selected Siah2-related transcripts, and Siah2 ubiquitin ligase activity. Several analogs were further characterized, demonstrating improved efficacy. Combination of the top hits identified in the different assays demonstrated an additive effect, pointing to complementing mechanisms that underlie each of these Siah1/2 inhibitors.
Synthetic Analogues of Betulinic Acid as Potent Inhibitors of PS1/BACE1 Interaction to Reduce Aβ Generation
Zhang, Chenlu,Wang, Xiaoyin,Cui, Jin,Li, Xiaohang,Zhang, Yangming,Wang, Xin,Gu, Haifeng,Li, Wei,Xie, Xin,Zhao, Jian,Pei, Gang,Nan, Fajun
, p. 103 - 112 (2017/02/05)
The lupane-type triterpenoids are endowed with a wide range of biological activities such as antiviral, anti-inflammatory and anticancer activity. We describe here its potential application in Alzheimer's disease (AD) treatment as an inhibitor of PS1/BACE1 interaction. 3-α-Akebonoic acid, which emanated from a high throughput screening (HTS), was discovered to interfere with PS1/BACE1 interaction and reduce amyloid β-protein (Aβ) production. In view of the limited source, we instead used naturally rich betulinic acid (compound 2) as starting material for lead optimization and a focused library of its derivatives was constructed to gain a better understanding of the structure activity relationship (SAR) of triterpenoid-type inhibitor of PS1/BACE1 interaction. Compound 22 was finally chosen as the most potent PS1/BACE1 interaction inhibitor, which reduced Aβ generation effectively.
