Design, synthesis and biological evaluation of tasiamide B derivatives as BACE1 inhibitors. Issue 9 (1st May 2015)

• Record Type: Journal Article
• Authors: Liu, Jian; Chen, Wuyan; Xu, Yechun; Ren, Sumei; Zhang, Wei; Li, Yingxia
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 9(2015)
• Page Start: 1963
• Page End: 1974
• Publication Date: 2015-05-01
• Subjects: Alzheimer's disease -- β-Secretase -- BACE1 inhibitor -- Synthesis -- Docking; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.03.034
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Nineteen new derivatives based on the structure of marine natural product tasiamide B were designed, synthesized, and evaluated for their inhibitory activity against BACE1, a potential therapeutic target for Alzheimer's disease. The hydrophobic substituents Val at P3 position, Leu at P1 ′ position, Ala at P2 ′ position, and Phe at P3 ′ position were found to significantly affect the inhibition. Free carboxylic acid at C-terminus was also found to be important to the activity. In addition, the structure–activity relationships (SARs) were supported by molecular docking simulation.