Identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screening

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.

Citation

Xu, Weijun and Chen, Gang and Zhu, Weiliang and Zuo, Zhili. 2010. Identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screening. Bioorganic & Medicinal Chemistry Letters. 20 (19): pp. 5763-5766.

Source Title

Bioorganic & Medicinal Chemistry Letters

DOI

10.1016/j.bmcl.2010.07.140

ISSN

0960-894X

School

School of Biomedical Sciences

Remarks

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

URI

http://hdl.handle.net/20.500.11937/9340

Collection

Curtin Research Publications