1. Synthesis of a C-galactopyranosyl-linked N-substituted 1,2-ethylenediamine
Uthai Sakee, Chiradet Nasuk Carbohydr Res. 2010 Jun 16;345(9):1222-4.doi: 10.1016/j.carres.2010.03.040.Epub 2010 Apr 8.
A straightforward route to a C-galactopyranosyl-linked 1,2-ethylenediamine is described. The five-step synthetic procedure involves: (i) C-allenylation of D-galactopyranose pentaacetate with propargyl trimethylsilane in the presence of a Lewis acid, (ii) iodination of allenyl galactopyranosyl tetraacetate to diiodoallyl galactopyranosyl tetraacetate, (iii) displacement of the allylic iodide with N-Boc-ethylenediamine, (iv) catalytic hydrogenation of vinyl iodide to alkane, (v) deprotection of the acetyl and N-Boc-groups using acid-catalyzed hydrolysis. This method demonstrates a general method to access a new class of carbohydrate-ethylenediamine C-glycosyl chelators.
2. Covalent tethering of organic functionality to the surface of glassy carbon electrodes by using electrochemical and solid-phase synthesis methodologies
Jean-Mathieu Chrétien, Mohamed A Ghanem, Philip N Bartlett, Jeremy D Kilburn Chemistry. 2008;14(8):2548-56.doi: 10.1002/chem.200701559.
Organic linkers such as (N-Boc-aminomethyl)phenyl (BocNHCH2C6H4) and N-Boc-ethylenediamine (Boc-EDA) have been covalently tethered onto a glassy carbon surface by employing electrochemical reduction of BocNHCH2C6H4 diazonium salt or oxidation of Boc-EDA. After removal of the Boc group, anthraquinone as a redox model was attached to the linker by a solid-phase coupling reaction. Grafting of anthraquinone to electrodes bearing a second spacer such as 4-(N-Boc-aminomethyl)benzoic acid or N-Boc-beta-alanine was also performed by following this methodology. The surface coverage, stability and electron transfer to/from the tethered anthraquinone redox group through the linkers were investigated by cyclic voltammetry. The effects of pH and scan rate were studied, and the electron-transfer coefficient and rate constant were determined by using Laviron's equation for the different types of linker. The combination of electrochemical attachment of protected linkers and subsequent modifications under the conditions of solid-phase synthesis provides a very versatile methodology for tailoring a wide range of organic functional arrangements on a glassy carbon surface.
3. Bruceine A induces cell growth inhibition and apoptosis through PFKFB4/GSK3β signaling in pancreatic cancer
Pengfei Zhang, Weiwei Tao, Cai Lu, Lu Fan, Qihang Jiang, Chengbin Yang, Erxin Shang, Haibo Cheng, Chuntao Che, Jinao Duan0, Ming Zhao Pharmacol Res. 2021 Jul;169:105658.doi: 10.1016/j.phrs.2021.105658.Epub 2021 May 14.
Pancreatic cancer is one of the most aggressive cancers with a poor prognosis and 5-year low survival rate. In the present study, we report that bruceine A, a quassinoid found in Brucea javanica (L.) Merr. has a strong antitumor activity against human pancreatic cancer cells both in vitro and in vivo. Human proteome microarray reveals that 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is the candidate target of bruceine A and both fluorescence measurement and microscale thermophoresis suggest bruceine A binds to PFKFB4. Bruceine A suppresses glycolysis by inhibiting PFKFB4, leading to cell cycle arrest and apoptosis in MIA PaCa-2 cells. Furthermore, glycogen synthase kinase-3 β (GSK3β) is identified as a downstream target of PFKFB4 and an PFKFB4-interacting protein. Moreover, bruceine A induces cell growth inhibition and apoptosis through GSK3β, which is dysregulated in pancreatic cancer and closely related to the prognosis. In all, these findings suggest that bruceine A inhibits human pancreatic cancer cell growth via PFKFB4/GSK3β-mediated glycolysis, and it may serve as a potent agent for curing human pancreatic cancer.
