Selected 1,3-benzodioxine-containing chalcones as multipotent monoamine oxidase and acetylcholinesterase inhibitors.

Selected 1,3-benzodioxine-containing chalcones as multipotent monoamine oxidase and acetylcholinesterase inhibitors. ChemMedChem. 2020 Sep 13;: Authors: Jeong GS, Kaipakasseri S, Lee SR, Marraiki N, Batiha GE, Dev S, Palakkathondi A, Kavully FS, Gambacorta N, Nicolotti O, Mathew B, Kim H Abstract Chalcones are considered effective templates for the development of monoamine oxidase (MAO) and cholinesterase (ChE) inhibitors. The present work describes the syntheses of selected 1,3-benzodioxine-containing chalcones (CD3, CD8 and CD10), and their inhibitory activities against MAO-A, MAO-B, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). Compound CD8 most potently inhibited MAO-B with an IC50 value of 0.026 µM, followed by CD10 and CD3 (1.54 and 1.68 µM, respectively). CD8 potently and non-selectively inhibited MAO-A (IC50 = 0.023 µM). On the other hand, CD10 and CD8 inhibited AChE with IC50 values of 5.40 and 9.57 µM, respectively. Kinetics and reversibility experiments showed that all synthesized molecules were competitive and reversible inhibitors, and the Ki values of CD8 for MAO-A and MAO-B were 0.018 and 0.0019 µM, respectively. By in vitro and in silico analyses, all compounds were found to have high passive human gastrointestinal absorptions, blood-brain barrier permeabilities, and non-toxicities. Molecular docking simulations revealed that docking affinity of each compound for MAO-B was higher than that for MA...
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research