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

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.

Piperidine: A Versatile Heterocyclic Ring for Developing Monoamine Oxidase Inhibitors

“…47 Currently, Food and Drug Administration (FDA)-approved drugs, such as antipsychotics, include haloperidol, 48 benperidol, 49 risperidone, 50 and thioridazine 51 for the symptomatic management of schizophrenia; droperidol, a dopamine antagonist used to prevent and treat postoperative nausea and vomiting; 52 and anticholinesterases, including donepezil 53 for treating AD (Figure 3). 26 Recently, many structural scaffolds, such as chalcones, 54 conjugated dienones, 55 isatins, 56 chromones, 57 coumarins, 58 pyrazolines, 59 quinazolines, 60 β-carbolines, 61 and benzyloxyderived molecules, 62 are used to develop MAO inhibitors. In search for newer MAO inhibitors, researchers have identified the inevitable role of halogens in selective and potent MAO-B inhibition.…”

“…MAO isozymes, namely, MAO-A and MAO-B, are each coded by respective genes on the X chromosome . Ammonia, aldehyde, and hydrogen peroxide are the three main intermediates produced through MAO-accelerated oxidative deamination. , MAO-A inhibitors are regarded as efficient therapeutic medicines for the treatment of neurological diseases, including anxiety and depression . MAO-B is one of the isozymes of MAO that is associated with neurodegeneration because its activity is markedly elevated in the brains of patients with AD .…”

“…Recently, many structural scaffolds, such as chalcones, conjugated dienones, isatins, chromones, coumarins, pyrazolines, quinazolines, β-carbolines, and benzyloxy-derived molecules, are used to develop MAO inhibitors. In search for newer MAO inhibitors, researchers have identified the inevitable role of halogens in selective and potent MAO-B inhibition .…”

“… 12 , 13 MAO-A inhibitors are regarded as efficient therapeutic medicines for the treatment of neurological diseases, including anxiety and depression. 14 MAO-B is one of the isozymes of MAO that is associated with neurodegeneration because its activity is markedly elevated in the brains of patients with AD. 15 MAO inhibitors, which are involved in the oxidative deamination pathway, might diminish the buildup of oxidative stress mediators, such as hydrogen peroxide, aldehydes, and ammonia, possibly slowing the progression of AD.…”

A Concise Review of the Recent Structural Explorations of Chromones as MAO-B Inhibitors: Update from 2017 to 2023

“…Specifically, MAO-A deaminates noradrenaline, whereas MAO-B preferentially deaminates phenylethylamine, serotonin (5-hydroxytryptamine), and benzylamine [ 22 ]. MAO-B is primarily present in glial cells in the brain [ 23 ], whereas MAO-A is found in noradrenergic, serotonergic, and dopaminergic nerves and extra-neuronal compartment terminals [ 24 ]. Specific MAO-B blockers have been employed with levodopa to treat PD, whereas specific MAO-A-inhibiting agents have been utilized as antidepressants and anxiolytics [ 25 , 26 , 27 , 28 ].…”