Synthesis and Monoamine Oxidase Inhibitory Activity of Halogenated Flavones

• Published in: ACS medicinal chemistry letters 2024-05, Vol.15 (5), p.610-618
• Main Authors: Castillo-Arellano, Jorge I., Stryker, Zachary, Wyatt, Michael D., León, Francisco
• Format: Article
• Language: English
• ISSN: 1948-5875; 1948-5875
• DOI: 10.1021/acsmedchemlett.3c00573

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.