Selective MAO-B inhibitors: a lesson from natural products

Abstract

Monoamine oxidases (MAOs) are mitochondrial bound enzymes, which catalyze the oxidative deamination of monoamine neurotransmitters. Inside the brain, MAOs are present in two isoforms: MAO-A and MAO-B. The activity of MAO-B is generally higher in patients affected by neurodegenerative diseases like Alzheimer's and Parkinson's. Therefore, the search for potent and selective MAO-B inhibitors is still a challenge for medicinal chemists. Nature has always been a source of inspiration for the discovery of new lead compounds. Moreover, natural medicine is a major component in all traditional medicine systems. In this review, we present the latest discoveries in the search for selective MAO-B inhibitors from natural sources. For clarity, compounds have been classified on the basis of structural analogy or source: flavonoids, xanthones, tannins, proanthocyanidins, iridoid glucosides, curcumin, alkaloids, cannabinoids, and natural sources extracts. MAO inhibition values reported in the text are not always consistent due to the high variability of MAO sources (bovine, pig, rat brain or liver, and human) and to the heterogeneity of the experimental protocols used.

Association between cigarette smoking and Parkinson’s disease: A meta-analysis

“…Recent studies have evaluated specific components of tobacco smoke for their MAO inhibiting and neuroprotective properties (Castagnoli & Murugesan, 2004;Berlin et al, 2012;Carradori et al, 2014).…”

Comparative study of biological activities and multicomponent pattern of two wild Turkish species: Asphodeline anatolica and Potentilla speciosa

“…Furthermore, phenolic compounds have recently received particular attention owing to their possible preventive role in neurological disorders [4][5][6][7] . In particular, recently Karioti and Gidaro 8,9 reviewed that phenolics represent the main interesting biological activities on unconventional targets, such as carbonic anhydrases, among plant secondary metabolites.…”

Synthesis of Amide and Ester Derivatives of Cinnamic Acid and Its Analogs: Evaluation of Their Free Radical Scavenging and Monoamine Oxidase and Cholinesterase Inhibitory Activities

“…Because of their potential neuroprotective effects, MAO-B inhibitors may be useful for the treatment of Alzheimer's disease. [6][7][8] Several natural and synthetic cinnamic acid amides and their esters were found to possess various biological properties such as antioxidant, 9,10) anti-inflammatory, 11) anti-tumor, 12) cytoprotective, 13,14) protection of β-amyloid protein aggregation, 15) tyrosinase inhibitory, 16,17) α-glucosidase inhibitory, 18,19) cholinesterase inhibitory, 20) and MAO inhibitory [21][22][23] activities. However, no systematically evaluated data are available on the antioxidant and MAO and ChE inhibitory activities of cinnamic acid derivatives.…”

“…1), and the structureactivity relationships (SARs) of the cinnamic acid derivatives with respect to antioxidant capacity and MAO and ChE inhibitory activities were investigated. feic acid, ferulic acid and p-coumaric acid were reacted with biogenic amines (i.e., serotonin, dopamine, tyramine, vanillylamine) to get amide compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), and with alcohols (i.e., 3,4-dihydroxyphenethylalcohol, 4-hydroxyphenethylalcohol, phenethylalcohol) to get ester compounds (13, 14, 16-22) (Chart 1). Their yields were satisfactory.…”