Synthesis and Monoamine Oxidase Inhibitory Activity of Halogenated Flavones

Small molecule neurotransmitters containing amines are metabolized by Monoamine Oxidase (MAO) in the nervous system. Monoamine Oxidase inhibitors are a valuable class of drugs prescribed for the management of neurological disorders, including depression. A series of halogenated Flavonoids similar to the dietary flavonoid acacetin were designed as selective MAO-B inhibitors. MAO-A and -B inhibition of 36 halogenated Flavones were tested. The halogens (fluorine and chlorine) were placed at positions 5 and 7 on ring A of the flavone scaffold. All compounds were selective MAO-B inhibitors with micro- and nanomolar IC₅₀ values. Compounds 9f, 10a-c, 11a-c, 11g,h, and 11l displayed inhibitory activity toward MAO-B with IC₅₀ values between 16 to 74 nM. We conclude that halogenated Flavonoids are promising molecules in pursuit of developing new agents for neurological disorders.