Review of β-carboline and its derivatives as selective MAO-A inhibitors

Arch Pharm (Weinheim). 2023 Jul;356(7):e2300091. doi: 10.1002/ardp.202300091. Epub 2023 Apr 6.

Abstract

As flavin adenine dinucleotide (FAD)-dependent enzymes, monoamine oxidases (MAOs) catalyze the oxidative deamination of various endogenous and exogenous amines. MAO-A inhibitors are thought to be effective therapeutic agents for treating neurological diseases including depression and anxiety. Due to the academic challenge of developing new human (h) MAO-A inhibitors and the potential for discovering substances with remarkable properties compared to existing MAO-A inhibitors, numerous research groups are looking into novel classes of chemical compounds that may function as selective hMAO-A inhibitors. β-Carbolines are reported to be a prominent class of bioactive molecules exhibiting MAO-A inhibition. Chemically, β-carboline is a tricyclic pyrido-3,4-indole ring. It has only recently been discovered that this chemotype has highly effective and specific MAO-A inhibitory activity. In this review, structure-activity relationship studies included in particular research publications from the 1960s to the present are discussed with regard to β-carboline and its analogs. This comprehensive information helps to design and develop a new family of MAO-A inhibitors for the management of depressive disorders.

Keywords: depression; harmine; monoamine oxidase-A; structure-activity relationship; β-carboline.

Publication types

  • Review

MeSH terms

  • Carbolines / chemistry
  • Carbolines / pharmacology
  • Humans
  • Monoamine Oxidase Inhibitors* / chemistry
  • Monoamine Oxidase Inhibitors* / pharmacology
  • Monoamine Oxidase* / metabolism
  • Structure-Activity Relationship

Substances

  • Monoamine Oxidase Inhibitors
  • norharman
  • Monoamine Oxidase
  • Carbolines