4-(O-Benzylphenoxy)-N-Methylbutylamine (Bifemelane) and Other 4-(O-Benzylphenoxy)-N-Methylalkylamines as New Inhibitors of Type A and B Monoamine Oxidase

4-(O-Benzylphenoxy)-N-methylbutylamine (Bifemelane, BP-N-methylbutylamine), a new psychotropic drug, was found to inhibit monoamine oxidase (MAO) in human brain synaptosomes. It inhibited type A MAO (MAO-A) competitively and type B (MAO-B) noncompetitively. BP-N-methylbutylamine had a much higher affinity to MAO-A than an amine substrate, kynuramine, and it was a more potent inhibitor of MAO-A than of MAO-B. The Ki values of MAO-A and -B were determined to be 4.20 and 46.0 microM, respectively, while the Km values of MAO-A and -B with kynuramine were 44.1 and 90.0 microM, respectively. The inhibition of MAO-A and -B by BP-N-methylbutylamine was found to be reversible by dialysis of the incubation mixture. MAO-A in human placental and liver mitochondria and in a rat clonal pheochromocytoma cell line, PC12h, was inhibited competitively by BP-N-methylbutylamine, while MAO-B in human liver mitochondria was inhibited noncompetitively, as in human brain synaptosomes. BP-N-methylbutylamine was not oxidized by MAO-A and -B. The effects of other BP-N-methylalkylamines, such as BP-N-methylethylamine, -propylamine, and -pentanylamine, on MAO activity were examined. BP-N-methylbutylamine was the most potent inhibitor of MAO-A, and BP-N-methylethylamine and -propylamine inhibited MAO-B competitively, whereas BP-N-methylbutylamine and -pentanylamine inhibited it noncompetitively. Inhibition of these BP-N-methylalkylamines on MAO-A and -B is discussed in relation to their chemical structure.     

Design and biological evaluation of phenyl-substituted analogs of beta-phenylethylidenehydrazine

Beta-Phenylethylidenehydrazine (PEH) has been demonstrated previously to be an inhibitor of gamma-aminobutyric acid transaminase (GABA-T) and to cause a marked increase in rat brain levels of GABA, a major neurotransmitter. A group of PEH analogs, possessing a variety of substituents (Me, OMe, Cl, F, and CF3) at the 2-, 3-, and 4-positions of the phenyl ring, were synthesized for evaluation as inhibitors of GABA-T. The details of the synthesis and chemical characterization of the analogs are described. Preliminary in vitro screening for GABA-T inhibition showed that all the analogs possessed activity against this enzyme, although substitution of CF3 at the 2- and 4-positions caused reduced activity. One of the drugs, 4-fluoro-beta-phenylethylidenehydrazine, was investigated further ex vivo, where it was shown to inhibit GABA-T, elevate brain levels of GABA, and decrease levels of glutamine, similar to the profile observed previously for PEH.     

Inhibition of Type A Monoamine Oxidase by Methylquinolines and Structurally Related Compounds

Abstract: A series of methylquinolines (MQ) were found to inhibit markedly type A monoamine oxidase (MAO) in human brain synaptosomal mitochondria. 4-MQ and 6-MQ inhibited type A MAO (MAO-A) competitively and 7- and 8-MQ inhibited MAO-A noncompetitively. Among these four isomers of MQ, 6-MQ was the most potent inhibitor; the K _i value toward MAO-A was 23.4 ± 1.8 μ M , which was smaller than the K _m value toward kynuramine, ± amine substrate, 46.2 ± 2.8 μ M . On the other hand, MQ were very weak inhibitors of type B MAO (MAO-B) and 8-MQ did not inhibit MAO-B in brain synaptosomal mitochondria. The inhibition of MAO-A proved to be reversible; by dialysis the inhibition of MQ was completely reversible. The affinity of these isomers of MQ toward MAO-A or -B was confirmed further with human liver mitochondria as sources of MAO-A and -B and with human placental mitochondria and rat pheochromocytoma PC12h cell line as sources of MAO-A. The relationship of the chemical structure of structurally related quinoline and isoquinoline derivatives to inhibition of the activity of type A or B MAO was examined.     

Human monoamine oxidase is inhibited by tobacco smoke: beta-carboline alkaloids act as potent and reversible inhibitors

Monoamine oxidase (MAO) is a mitochondrial outer-membrane flavoenzyme involved in brain and peripheral oxidative catabolism of neurotransmitters and xenobiotic amines, including neurotoxic amines, and a well-known target for antidepressant and neuroprotective drugs. Recently, positron emission tomography imaging has shown that smokers have a much lower activity of peripheral and brain MAO-A (30%) and -B (40%) isozymes compared to non-smokers. This MAO inhibition results from a pharmacological effect of smoke, but little is known about its mechanism. Working with mainstream smoke collected from commercial cigarettes we confirmed that cigarette smoke is a potent inhibitor of human MAO-A and -B isozymes. MAO inhibition was partly reversible, competitive for MAO-A, and a mixed-type inhibition for MAO-B. Two beta-carboline alkaloids, norharman (beta-carboline) and harman (1-methyl-beta-carboline), were identified by GC-MS, quantified, and isolated from the mainstream smoke by solid phase extraction and HPLC. Kinetics analysis revealed that beta-carbolines from cigarette smoke were competitive, reversible, and potent inhibitors of MAO enzymes. Norharman was an inhibitor of MAO-A (K(i)=1.2+/-0.18 microM) and MAO-B (K(i)=1.12+/-0.19 microM), and harman of MAO-A (K(i)=55.54+/-5.3nM). Beta-carboline alkaloids are psychopharmacologically active compounds that may occur endogenously in human tissues, including the brain. These results suggest that beta-carboline alkaloids from cigarette smoke acting as potent reversible inhibitors of MAO enzymes may contribute to the MAO-reduced activity produced by tobacco smoke in smokers. The presence of MAO inhibitors in smoke like beta-carbolines and others may help us to understand some of the purported neuropharmacological effects associated with smoking.     

Formation of the Neurotransmitter Glycine from the Anticonvulsant Milacemide Is Mediated by Brain Monoamine Oxidase B

Milacemide (2-n-pentylaminoacetamide) is a secondary monoamine that in the brain is converted to glycinamide and glycine. This oxidative reaction was suspected to involve the reaction of monoamine oxidase (MAO). Using mitochondrial preparations from tissues that contain MAO-A and -B (rat brain and liver), MAO-A (human placenta), and MAO-B (human platelet and bovine adrenal chromaffin cell), it has been established that mitochondria containing MAO-B rather than MAO-A oxidize (H2O2 production and glycinamide formation) milacemide. The apparent Km (30-90 microM) for milacemide oxidation by mitochondrial MAO-B preparations is significantly lower than that for milacemide oxidation by mitochondrial MAO-A (approximately 1,300 microM). In vitro MAO-B (l-deprenyl and AGN 1135) rather than MAO-A (clorgyline) selectively inhibited the oxidation of milacemide. These in vitro data are matched by ex vivo experiments where milacemide oxidation was compared to oxidation of serotonin (MAO-A) and beta-phenylethylamine (MAO-B) by brain mitochondria prepared from rats pretreated with clorgyline (0.5-10 mg/kg) and l-deprenyl (0.5-10 mg/kg). Furthermore, in vivo experiment demonstrated that l-deprenyl selectively increased the urinary excretion of [14C]milacemide and the total radioactivity with a concomitant decrease of [14C]glycinamide. Such changes were not observed after clorgyline treatment, but were evident only at doses beyond clorgyline selectivity. The present data therefore demonstrate that milacemide is a substrate for brain MAO-B, and its conversion to glycinamide, further transformed to the inhibitory neurotransmitter, glycine, mediated by this enzyme may contribute to its pharmacological activities.     

Quinoline and quninaldine as naturally occurring inhibitors specific for type A monoamine oxidase

Type A monoamine oxidase (MAO-A) in human placental mitochondria was competitively inhibited by naturally occurring substances, quinoline and quinaldine, using kynuramine as substrate. Quinoline had a higher affinity for MAO than kynuramine. MAO-A in human brain synaptosomal mitochondria was also competitively inhibited by quinoline, while type B MAO (MAO-B) was reversibly and non-competitively inhibited by quinoline. Quinoline inhibited MAO-A much more potently than MAO-B. Of several compounds structurally similar to quinoline, isoquinoline noncompetitively inhibited MAO-A and -B activity.     

Effect of chlorpromazine, imipramine and lithium on MAO-A and MAO-B activity in rat brain mitochondria

Drugs with efficacy in psychiatric disorders affect the function of central neurotransmitter amines, which are inactivated primarily by monoamine oxidase (MAO). Effect of these drugs on the two types of MAO (MAO-A and MAO-B) has been studied in rat brain. The result showed that chlorpromazine (CPZ) and imipramine (IMI) at concentrations of 1x10(-2), 5x10(-3) and 2.5x10(-3) M inhibited rat brain mitochondrial MAO-A activity in vitro by 82, 50, 39 and 86, 74, 38 %, respectively. CPZ at concentrations of 5x10(-3), 2.5x10(-3), 1x10(-3) M inhibited rat brain mitochondrial MAO-B activity in vitro by 83, 55, 39 %, respectively, while IMI at concentrations of 5x10(-4), 2.5x10(-4), 1x10(-4) M inhibited the in vitro enzyme activity by 43, 35, 21 %, respectively. Lithium at concentration of 5x10(-3) M could not either inhibit MAO-A or MAO-B in the mitochondrial fraction of rat brain.     

Inhibitory effects of cis- and trans-resveratrol on noradrenaline and 5-hydroxytryptamine uptake and on monoamine oxidase activity

This study investigated for the first time the potential effects of cis- and trans-resveratrol (c-RESV and t-RESV) on noradrenaline (NA) and 5-hydroxytryptamine (5-HT) uptake by synaptosomes from rat brain, on 5-HT uptake by human platelets, and on monoamine oxidase (MAO) isoform activity. Both c-RESV and t-RESV (5-200 microM) concentration-dependently inhibited the uptake of [3H]NA and [3H]5-HT by synaptosomes from rat brain and the uptake of [3H]5-HT by human platelets. In both experimental models, t-RESV was slightly more efficient than c-RESV. Furthermore, in synaptosomes from rat brain, the RESV isomers were less selective against [3H]5-HT uptake than the reference drug fluoxetine (0.1-30 microM). On the other hand, both c-RESV and t-RESV (5-200 microM) concentration-dependently inhibited the enzymatic activity of commercial (human recombinant) MAO isoform (MAO-A and MAO-B) activity, c-RESV being slightly less effective than t-RESV. In addition, both RESV isomers were slight but significantly more selective against MAO-A than against MAO-B. Since the principal groups of drugs used in the treatment of depressive disorders are NA/5-HT uptake or MAO inhibitors, under the assumption that the RESV isomers exhibit a similar behaviour in humans in vivo, our results suggest that these natural polyphenols may be of value as structural templates for the design and development of new antidepressant drugs with two important biochemical activities combined in the same chemical structure: NA/5-HT uptake and MAO inhibitory activity.     

Biochemistry and physiology of monoamine oxidase (MAO) activity in the ring dove (Streptopelia risoria). II. Distribution of MAO in different tissues

Monoamine oxidase (MAO) activity was measured fluorometrically in liver, kidney, intestine and brain of adult male and female ring doves. Liver MAO was inhibited in a concentration-related fashion by clorgyline and harmaline (MAO type A inhibitors) where a plateau in the inhibition curve occurred with about 15% activity remaining, and also by the type B inhibitor deprenyl, which produced a plateau when about 85% activity remained. Kidney, intestine and brain MAO were inhibited in a biphasic manner by harmaline. Results with inhibitors suggest that 85% of liver MAO, 86% of kidney MAO, 88% of intestine and 75% of brain MAO is type A. Using 10(-6) M harmaline to differentiate between MAO-A and MAO-B type activities, the apparent maximal velocities (Vmax) and Michaelis constants (Km) were determined in different tissues. Most activity occurred in the intestine, with proportionally lesser amounts of kidney, liver and brain. The majority of MAO present was in the A form. Except for kidney, Km of MAO-B was higher than that of MAO-A. Both MAO-A and -B activities were higher in the intestines of male birds, although sex differences in content and type of MAO activity were not observed in other tissues of the ring dove.     

Inhibition of Monoamine Oxidase by 3,4-Dihydroxyphenylserine

The effects of diastereomers of 3,4-dihydroxyphenylserine (DOPS) on the enzyme activity of monoamine oxidase (MAO) in human placenta and liver mitochondria were examined. Both L- and D-threo-DOPS were found to inhibit MAO-A in human placental mitochondria in competition with the substrate, and the Ki values for L- and D-threo-DOPS obtained were 68.3 and 125 microM, respectively. The inhibitory effect of L-threo-DOPS on both MAO-A and -B activity was confirmed in human liver mitochondria, and MAO-A was found to be more sensitive to the inhibitor. Other isomers of DOPS, L- and D-erythro-DOPS, were found to inhibit MAO activity, but the inhibition was noncompetitive with the substrate. The inhibitory effects of DOPS isomers were not affected by the presence of NSD-1055, an inhibitor of aromatic L-amino acid decarboxylase, suggesting that the inhibition is the direct effect of DOPS, and not of norepinephrine produced by the decarboxylase.     

Selective inhibition of MAO-A in serotonergic synaptosomes by two amphetamine metabolites, p-hydroxyamphetamine and p-hydroxynorephedrine

The present study was carried out mainly to clarify whether the two amphetamine metabolites, p-hydroxyamphetamine (P-OHA) and p-hydroxynorephedrine (p-OHN) are taken up by mouse brain 5-hydroxytryptamine (5-HT) nerve terminals to inhibit type A monoamine oxidase (MAO-A) and then potentiate the abnormal behavior, head-twitch. Of the two metabolites, only intracerebroventricular p-OHA, at 80 μg/mouse, sufficient to cause a head-twitch response (HTR), appreciably inhibited MAO-A activity without affecting MAO-B activity in homogenates of the mouse striatum, hypothalamus and the rest of the forebrain; and p-OHN did not inhibit either type of MAO at the dose tested. Estimation of intra- and extrasynaptosomal MAO-A activity showed that both metabolites significantly inhibited only the intrasynaptosomal deamination of 5-HT by MAO-A with p-OHA being more potent. Taken together with our previous findings, these present results clearly indicate that p-OHA may accumulate in the 5-HT nerve terminals through the uptake system, and concomitantly inhibit MAO-A activity. These actions of p-OHA may increase intraneuronal 5-HT levels and then potentiate 5-HT release to cause interaction with the post-synaptic 5-HT receptors.     

Inhibition of Monoamine Oxidase by N-Methylisoquinolinium Ion

N-Methylisoquinolinium ion (N-MIQ) has been found to inhibit the biosynthesis of catecholamines; it inhibited tyrosine hydroxylase activity in striatal tissue slices. In this article, the effects of N-MIQ and an analogue, N-methylquinolinium ion, on monoamine oxidase (MAO) activity were examined to see their effects on the catabolism of catecholamines. MAO-A in human placental mitochondria was strongly inhibited by N-MIQ in competition with the substrate. The apparent Ki value of N-MIQ was found to be 20.4 +/- 1.1 microM, whereas that of N-methylquinolinium ion was 54.6 +/- 4.5 microM. MAO-B in human brain synaptosomes and liver mitochondria was found to be inhibited by N-MIQ, but the inhibition proved to be noncompetitive. The inhibition of MAO-B by N-MIQ was completely reversible by dialysis of the incubation mixture. MAO-A in human brain and liver mitochondria was more sensitive to the inhibitor than MAO-B. By quantitative analysis of N-MIQ, using HPLC, it was found not to be catabolized by the incubation with mitochondria, suggesting that the inhibition was due to N-MIQ itself and not due to any metabolic product. The inhibition of MAO by N-MIQ is discussed in terms of its possible involvement of the etiology of parkinsonism.     

Monoamine oxidase and semicarbazide-sensitive amine oxidase in spontaneously hypertensive and in normotensive control rats

The aim of the present work was to compare monoamine oxidase (MAO) and semicarbazide sensitive amine oxidase (SSAO) activity in several tissues from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY). Contribution of MAO-A, -B and SSAO to the metabolism of each substrate in each tissue was defined from experiments where the decrease of oxidative deamination of each substrate at a given concentration was measured as a function of increasing concentrations of a selective MAO-A, -B or SSAO inhibitor. In the heart, aorta and, to a lesser extent, the femoral arteries MAO-A activity was higher in SHR than in WKY. Similarly in the liver the enzyme activity was higher in SHR than in WKY but was due to the -B form of MAO. In all the other tissues studied (duodenum, brain, lungs, adrenals and kidneys) no difference in MAO-A, MAO-B or SSAO activity was found between SHR and WKY, except for the kidneys and brain, if the differences in the weights of these organs in SHR are taken into account.     

Calcium disodium edetate enhances type A monoamine oxidase activity in monkey brain

The effects of metal chelators on monoamine oxidase (MAO) isozymes, MAO-A and MAO-B, in monkey brain mitochondria were investigated in vitro. MAO-A activity increased to about 40% with 0.1 μM calcium disodium edetate (CaNa₂EDTA) using serotonin as a substrate, and this activation was proportional to the concentration of CaNa₂EDTA. On the other hand, MAO-A activities were decreased gradually with an increasing concentration of o-phenanthroline and diethyldithiocarbamic acid, but these metal chelators had no effect on MAO-B activity in monkey brain. The activation of MAO-A activity by CaNa₂EDTA was reversible. CaNa₂EDTA did not activate both MAO-A and MAO-B activities in rat brain mitochondria. Zn and Fe ions were found in the mitochondria of monkey brain. Zn ions potently inhibited MAO-A activity, but Fe ions did not inhibit either MAO-A or MAO-B activity in monkey brain mitochondria. These results indicate that the activating action of CaNa₂EDTA on MAO-A was the result of the chelating of Zn ions contained in mitochondria by CaNa₂EDTA. These results also indicate the possibility that Zn ions may regulate physiologically the level of serotonin and norepinephrine content in brain by inhibiting a MAO-A activity.     

Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases: in vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition

Iron-dependent oxidative stress, elevated levels of iron and of monoamine oxidase (MAO)-B activity, and depletion of antioxidants in the brain may be major pathogenic factors in Parkinson's disease, Alzheimer's disease and related neurodegenerative diseases. Accordingly, iron chelators, antioxidants and MAO-B inhibitors have shown efficacy in a variety of cellular and animal models of CNS injury. In searching for novel antioxidant iron chelators with potential MAO-B inhibitory activity, a series of new iron chelators has been designed, synthesized and investigated. In this study, the novel chelators were further examined for their activity as antioxidants, MAO-B inhibitors and neuroprotective agents in vitro. Three of the selected chelators (M30, HLA20 and M32) were the most effective in inhibiting iron-dependent lipid peroxidation in rat brain homogenates with IC50 values (12-16 microM), which is comparable with that of desferal, a prototype iron chelator that is not has orally active. Their antioxidant activities were further confirmed using electron paramagnetic resonance spectroscopy. In PC12 cell culture, the three novel chelators at 0.1 microM were able to attenuate cell death induced by serum deprivation and by 6-hydroxydopamine. M30 possessing propargyl, the MAO inhibitory moiety of the anti-Parkinson drug rasagiline, displayed greater neuroprotective potency than that of rasagiline. In addition, in vitro, M30 was a highly potent non-selective MAO-A and MAO-B inhibitor (IC50 < 0.1 microM). However, HLA20 was more selective for MAO-B but had poor MAO inhibition, with an IC50 value of 64.2 microM. The data suggest that M30 and HLA20 might serve as leads in developing drugs with multifunctional activities for the treatment of various neurodegenerative disorders.     

Modification of substrate-inhibitor affinities of human platelet monoamine oxidase B in vitro

The rate of benzylamine utilization by monoamine oxidase (MAO)-B from human blood platelets was 2-4 times higher than that for octopamine. Both activities were inhibited 100% by 10(-7) M deprenyl (a specific MAO-B inhibitor) and were not affected by clorgyline (a specific MAO-A inhibitor) or by polyclonal antibodies to MAO-A. The preincubation of platelet MAO-B with purified MAO-A from mitochondrial membranes of human placenta resulted in appearance of excess octopamine activity. This additional activity was not precipitated by antibodies to MAO-A or inhibited by deprenyl but was inhibited by clorgyline. Incubation of the MAO-A preparation from placenta at 45 degrees C for 15 min before its preincubation with MAO-B caused 50% loss of both activities. Protease inhibitors had no effect on the modification of MAO. These data indicate that MAO-A or a factor tightly bound to it can modify MAO-B yielding a form of the enzyme with both MAO-A and MAO-B substrate and inhibitor affinities and MAO-B immunospecificity.     

Attenuation of MPTP-induced dopaminergic neurotoxicity by TV3326, a cholinesterase-monoamine oxidase inhibitor

(R)-[(N-propargyl-(3R) aminoindan-5-yl) ethyl methyl carbamate] (TV3326) is a novel cholinesterase and brain-selective monoamine oxidase (MAO)-A/-B inhibitor. It was developed for the treatment of dementia co-morbid with extra pyramidal disorders (parkinsonism), and depression. On chronic treatment in mice it attenuated striatal dopamine depletion induced by MPTP and prevented the reduction in striatal tyrosine hydroxylase activity, like selective B and non-selective MAO inhibitors. TV3326 preferentially inhibits MAO-B in the striatum and hippocampus, and the degree of MAO-B inhibition correlates with the prevention of MPTP-induced dopamine depletion. Complete inhibition of MAO-B is not necessary for full protection from MPTP neurotoxicity. Unlike that seen after treatment with other MAO-A and -B inhibitors, recovery of striatal and hippocampal MAO-A and -B activities from inhibition by TV3326 did not show first-order kinetics. This has been attributed to the generation of a number of metabolites by TV3326 that cause differential inhibition of these enzymes. Inhibition of brain MAO-A and -B by TV3326 resulted in significant elevations of dopamine, noradrenaline and serotonin in the striatum and hippocampus. This may explain its antidepressant-like activity, resembling that of moclobemide in the forced-swim test in rats.     

Serotonin and benzylamine oxidation by type A and type B MAO of rat brain in presence of organophosphate pesticides

Organophosphate (OP) pesticides, monocrotophos (MCP), dichlorvos (DDVP) and phosphamidon significantly inhibit both MAO-A and MAO-B activities in rat brain mitochondria. The inhibition of MAO-A by MCP is reversible whereas the inhibition by DDVP and phosphamidon is irreversible. MAO-B is inhibited irreversibly by all these organophosphates suggesting that the mechanism of action of OP pesticides is through phosphorylation of serine residue present in active centre of MAO.     

Monoamine Oxidase-Inhibiting Properties of SR 95191, a New Pyridazine Derivative, in the Rat: Evidence for Selective and Reversible Inhibition of Monoamine Oxidase Type A In Vivo but Not In Vitro

In rodents, SR 95191 [3-(2-morpholinoethylamino)-4-cyano-6-phenylpyridazine] has been shown to be active in animal models of depression. The profile of activity of SR 95191 suggests that the compound is a selective and short-acting type A monoamine oxidase (MAO) inhibitor (MAOI) in vivo. In the present study, the interaction of SR 95191 with MAO-A and MAO-B activity was further examined in vivo and in vitro. In brain, liver, and duodenum of pretreated rats, SR 95191 selectively inhibited MAO-A (ED50 = 3-5 mg/kg, p.o.), whereas MAO-B was only weakly inhibited for doses as high as 300 mg/kg, p.o. In vivo, SR 95191 (1-100 mg/kg, p.o.) antagonized, in a dose-dependent fashion, the irreversible inhibition of brain and liver MAO-A induced by phenelzine. Finally, dopamine and 5-hydroxytryptamine depleted from their striatal stores by tetrabenazine were able to displace SR 95191 from the active site of MAO-A. However, ex vivo, kinetic studies showed that the inhibitory effect of SR 95191 (1-10 mg/kg) towards MAO-A was noncompetitive and was unchanged after dilution or dialysis. In vitro, the inhibition of brain MAO-A, but not MAO-B, by SR 95191 was time dependent, with a 19-fold decrease in the IC50 values being observed over a 30-min incubation period (140 to 7.5 microM). At this time, the SR 95191-induced inhibition of MAO-A was not removed by repeated washings. When the reaction was started by adding the homogenate without prior preincubation with SR 95191, the inhibition of brain MAO-A was fully competitive (Ki = 68 microM).(ABSTRACT TRUNCATED AT 250 WORDS)     

Synthesis, molecular modeling studies, and selective inhibitory activity against monoamine oxidase of N,N'-bis[2-oxo-2H-benzopyran]-3-carboxamides

A novel series of N,N'-bis[2-oxo-2H-1-benzopyran]-3-carboxamide derivatives have been synthesized and investigated for the ability to inhibit the activity of the A and B isoforms of monoamine oxidase (MAO). Some of the synthesized compounds show good selective inhibitory activity against the MAO-A isoform. Both the MAO-A and -B isoforms, deposited in the Protein Data Bank as the 2BXR and 1GOS models, respectively, were considered in a computational study performed with docking techniques on the most active and selective inhibitors.