Identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screening
MetadataShow full item record
Nowadays identification of novel non-peptide β-secretase (BACE-1, hereinafter) inhibitors with low cytotoxicity and good blood–brain barrier (BBB) property holds common interest of drug discovery for Alzheimer’s disease. Twenty SPECS compounds were tested in BACE-1 FRET assays and methylthiazoletetrazolium (MTT) cytotoxicity experiment. Two compounds: 2 and 15 demonstrated IC50 values of 0.53 and 9.4 μM. In addition, 2 showed least toxic effect to the neuroblastoma cells. The results from both in silico and in vitro studies provided new pharmacophoric entities for chemical synthesis and optimization on the current discovered BACE-1 small molecule inhibitors.
NOTICE: this is the author’s version of a work that was accepted for publication in Bioorganic & Medicinal Chemistry Letters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Bioorganic & Medicinal Chemistry Letters [20, 19, 2010] DOI 10.1016/j.bmcl.2010.07.140
Showing items related by title, author, creator and subject.
Carbon-tolerant Ni-based cermet anodes modified by proton conducting yttrium- and ytterbium-doped barium cerates for direct methane solid oxide fuel cellsLi, M.; Hua, B.; Luo, J.; Jiang, San Ping; Pu, J.; Chi, B.; Jian, L. (2015)© The Royal Society of Chemistry. Conventional Ni-based cermet anodes such as Ni-gadolinia doped ceria (Ni-GDC) suffer from low carbon deposition resistance in direct methane solid oxide fuel cells (SOFCs). Here we show ...
Molecular docking and structure-activity relationship studies on benzothiazole based non-peptidic BACE-1 inhibitorsXu, W.; Chen, G.; Zhu, W.; Zuo, Zhili (2010)A similarity search on the structural analogs of an inhibitor of BACE-1 with IC50 2.8 μM, which contained a P1 benzothiazole group together with a triazine ring linked by a secondary amine group, was described in this ...
Stable and easily sintered BaCe0.5Zr0.3Y0.2O3-delta electrolytes using ZnO and Na2CO3additives for protonic oxide fuel cellsLi, Y.; Guo, R.; Wang, C.; Liu, Y.; Shao, Zongping; An, J.; Liu, C. (2013)BaCe0.5Zr0.3Y0.2O3-delta (BCZY) based composite electrolyte materials were fabricated with ZnO sintering aid (BCZY-Z). The effects of Na2CO3 modification on sintering behavior, chemical stability and electrochemical ...