TY - JOUR

T1 - Monoamine oxidase inhibition properties of 2,1-benzisoxazole derivatives

AU - Shetnev, Anton

AU - Kotov, Alexandr

AU - Kunichkina, Anna

AU - Proskurina, Irina

AU - Baykov, Sergey

AU - Korsakov, Mikhail

AU - Petzer, Anél

AU - Petzer, Jacobus P.

N1 - Shetnev, A., Kotov, A., Kunichkina, A. et al. Monoamine oxidase inhibition properties of 2,1-benzisoxazole derivatives. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10628-4

PY - 2023/3/19

Y1 - 2023/3/19

N2 - Monoamine oxidase (MAO) are flavoenzymes that metabolize neurotransmitter, dietary and xenobiotic amines to their corresponding aldehydes with the production of hydrogen peroxide. Two isoforms, MAO-A and MAO-B, are expressed in humans and mammals, and display different substrate and inhibitor specificities as well as different physiological roles. MAO inhibitors are of much therapeutic value and are used for the treatment of neuropsychiatric and neurodegenerative disorders such as depression, anxiety disorders, and Parkinson’s disease. To discover MAO inhibitors with good potencies and interesting isoform specificities, the present study synthesized a series of 2,1-benzisoxazole (anthranil) derivatives and evaluated them as in vitro inhibitors of human MAO. The compounds were in most instances specific inhibitors of MAO-B with the most potent MAO-B inhibition observed for 7a (IC50 = 0.017 µM) and 7b (IC50 = 0.098 µM). The most potent MAO-A inhibition was observed for 3l (IC50 = 5.35 µM) and 5 (IC50 = 3.29 µM). It is interesting to note that 3-(2-aminoethoxy)-1,2-benzisoxazole derivatives, the 1,2-benzisoxazole, zonisamide, as well as the isoxazole compound, leflunomide, have been described as MAO inhibitors. This is however the first report of MAO inhibition by derivatives of the 2,1-benzisoxazole structural isomer.

AB - Monoamine oxidase (MAO) are flavoenzymes that metabolize neurotransmitter, dietary and xenobiotic amines to their corresponding aldehydes with the production of hydrogen peroxide. Two isoforms, MAO-A and MAO-B, are expressed in humans and mammals, and display different substrate and inhibitor specificities as well as different physiological roles. MAO inhibitors are of much therapeutic value and are used for the treatment of neuropsychiatric and neurodegenerative disorders such as depression, anxiety disorders, and Parkinson’s disease. To discover MAO inhibitors with good potencies and interesting isoform specificities, the present study synthesized a series of 2,1-benzisoxazole (anthranil) derivatives and evaluated them as in vitro inhibitors of human MAO. The compounds were in most instances specific inhibitors of MAO-B with the most potent MAO-B inhibition observed for 7a (IC50 = 0.017 µM) and 7b (IC50 = 0.098 µM). The most potent MAO-A inhibition was observed for 3l (IC50 = 5.35 µM) and 5 (IC50 = 3.29 µM). It is interesting to note that 3-(2-aminoethoxy)-1,2-benzisoxazole derivatives, the 1,2-benzisoxazole, zonisamide, as well as the isoxazole compound, leflunomide, have been described as MAO inhibitors. This is however the first report of MAO inhibition by derivatives of the 2,1-benzisoxazole structural isomer.

KW - Monoamine oxidase

KW - MAO

KW - inhibition

KW - 2,1-benzisoxazole

KW - specificity

UR - https://link.springer.com/article/10.1007/s11030-023-10628-4

M3 - Article

JO - Molecular Diversity

JF - Molecular Diversity

SN - 1381-1991

ER -