MAO inhibitory activity of bromo-2-phenylbenzofurans: synthesis, in vitro study, and docking calculations

摘要: Monoamine oxidase (MAO) is an enzyme responsible for metabolism of monoamine neurotransmitters which play important role in brain development and function. This exists two isoforms, it has been demonstrated that MAO-B activity, but not MAO-A increases with aging. MAO inhibitors show clinical value because besides the level regulation they reduce formation by-products catalytic cycle, are toxic to brain. A series 2-phenylbenzofuran derivatives was designed, synthesized evaluated against hMAO-A hMAO-B enzymes. bromine substituent introduced 2-phenyl ring, whereas position 5 or 7 benzofuran moiety substituted a methyl group. Most tested compounds inhibited preferentially reversible manner, IC50 values low micro nanomolar range. The 2-(2′-bromophenyl)-5-methylbenzofuran (5) most active compound identified (IC50 = 0.20 μM). In addition, none studied showed cytotoxic activity human neuroblastoma cell line SH-SY5Y. Molecular docking simulations were used explain observed structure–activity relationship this type compounds.