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Dr. Bijo Mathew Prof. Dr. Gülberk Uçar Githa Elizabeth Mathew Sincy Mathew Praseedha Kalatharakkal Purapurath Fasil Moolayil Smrithy Mohan Dr. Sheeba Varghese Gupta 《ChemMedChem》2016,11(24):2649-2655
Numerous studies have shown that chalcones are promising scaffolds for the development of new monoamine oxidase‐B (MAO‐B) inhibitors. As a continuation of our ongoing research into the development of reversible human MAO‐B (hMAO‐B) inhibitors, two series of twenty chalcones containing electron‐donating and electron‐withdrawing substituents were synthesized. All compounds were found to be competitive, selective, and reversible inhibitors of hMAO‐B except (2E)‐1‐(4‐methylphenyl)‐3‐(4‐nitrophenyl)prop‐2‐en‐1‐one ( P7 ) and (2E)‐1‐(4‐chlorophenyl)‐3‐(4‐nitrophenyl)prop‐2‐en‐1‐one ( P17 ), which were found to be selective inhibitors of hMAO‐A. The most potent hMAO‐B inhibitor, (2E)‐1‐(4‐chlorophenyl)‐3‐(4‐ethylphenyl)prop‐2‐en‐1‐one ( P16 ), showed a Ki value of 0.11±0.01 μm . Molecular docking simulations were carried out to identify the hypothetical binding mode for the most potent compounds in the active sites of hMAO‐A and B. The ability of the compounds to cross the blood–brain barrier was assessed by parallel artificial membrane permeability assay (PAMPA). Additionally, the most potent hMAO‐B inhibitor P16 showed no toxicity in cultured hepatic cells at concentrations of 5 and 25 μm . 相似文献
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