Synthesis and evaluation of arylquinones as BACE1 inhibitors, β-amyloid peptide aggregation inhibitors, and destabilizers of preformed β-amyloid fibrils

Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues

“…All the juglone derivatives (NQ7 to NQ15) were prepared according to methods described in the literature [14]. Juglone (NQ7) is a commercial material and, when needed on a large scale, was prepared according to the method by Tietze et al [42] and purified by flash chromatography [14,43,44]. Acetylation of juglone under standard conditions yielded juglone acetate (5-acetoxy-1,4-naphthoquinone, NQ8) [45].…”

Palladium‐Catalyzed Direct CH Functionalization of Benzoquinone

“…Having developed an efficient Pd‐catalyzed direct CH monofunctionalization of BQ, we sought to extend this to a controlled CH difunctionalization. Diarylated BQs have found diverse uses as ligands,8 in molecular electronics,4b natural products,23 and biologically active compounds,24 despite their multi‐step syntheses, which are often restricted to homo‐disubstituted BQs 2. 25 We first explored a one‐pot homo‐difunctionalization (R=R′ in Scheme ).…”

Design, synthesis and biological evaluation of tasiamide B derivatives as BACE1 inhibitors

“…Therefore, the core structure of series I derivatives for BACE1 inhibition comprises a 6-residue acyclic peptide containing Val at P 3 position, Ahppa at P 1 position, Leu at P 1 0 position, Ala at P 2 0 position, Phe at P 3 0 position, and Gln at P 2 position connecting Val and Ahppa residues. Considering the SARs of the series I, the C-terminus was substituted by Ahppa, Leu, Ala and Phe residues, and the N-terminus was replaced with different hydrophobic substituent, with the aim of forming more strong hydrophobic interaction with S 3 sub-pocket in series II (Table 1, [13][14][15][16][17][18][19][20][21]. Among these compounds, replacing of the phenyl at the P 2 position with the electron-deficient pyridine caused significant decrease of activity (16 vs 15, and 18 vs 17).…”

“…[10][11][12][13][14] Over the past decade, a large number of peptidic and pseudopeptidic BACE1 inhibitors have been reported. [15][16][17][18][19][20][21][22][23][24][25] Most of these inhibitors comprised a statine (c-amino-b-hydroxy acid) residue, which formed hydrogen bonding interactions with two aspartic acids in the catalytic site. Tang and coworkers described the X-ray crystal structure of a large peptidic inhibitor OM99-2 (K i = 1.6 nM, Fig.…”