MAOIs Research Articles

Design, synthesis, and evaluation of 1, 4-benzodioxan-substituted chalcones as selective and reversible inhibitors of human monoamine oxidase B

The inhibition of monoamine oxidase B (MAO-B) could be an effective approach for the treatment of various neurological disorders. In this study, a series of 1, 4-benzodioxan-substituted chalcone derivatives were designed, synthesised and evaluated for their inhibitory activity against human MAO-B (hMAO-B). The majority of these compounds showed inhibitory activity and high selectivity. The most potent compound, (E)-1-(3-bromo-4-fluorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)prop-2-en-1-one (22), exhibited an IC50 of 0.026 µM with a selectivity index greater than 1538. Kinetics and reversibility studies confirmed that the representative active compounds acted as competitive and reversible inhibitors of hMAO-B. The enzyme-inhibitor interactions were investigated by molecular docking studies and the rationale was provided. As these potent hMAO-B inhibitors exhibited low neurotoxicity and possessed promising drug-like properties, we believe that these active compounds could be further investigated as potential drug candidates for future in vivo studies.

4, 5-Dihydro-1H-Pyrazol-1-YL Derivatives as MAO-A Inhibitors with Antidepressant Profile: Insilico Design and Docking

Mono Amine Oxidase-A will be a key controller for typical brain activity. It is a flavoenzyme which debases amines, for example, dopamine, norepinephrine, and serotonin, by means of oxidative deamination. Main focal point of the existent research work is to design, docking and biological screening of novel Pyrazole derivatives on MAO-A as Antidepressants. In our present study we used software’s like ACD chemsketch and biological data bases like Protein Data Bank (PDB). ACD/Chem sketch (v 14.00) to draw molecules, reactions and schematic diagrams, calculate chemical properties and design professional reports and presentation. Also it can produce SMILES notations to structure. Open babel converts SMILES to PDB file for docking. Receptors like 2z5x, 2z5y, 2bxs 6fvz, 2bxr are downloaded from the Protein Data Bank (PDB). Docking studies were performed on docking Server. In order to explore their binding mode and selectivity behavior, molecular docking in the active site of MAO-A was carried out for these derivatives. Analysis of the docked poses of the compounds showed that they adopt similar conformations to the highly selective MAO-A inhibitor. The docking pose of compound with 2BXR was confirmed by molecular dynamics. By all these in silico data, it can be confirmed that all the designed compounds are having drug like nature and suitable as drug candidates and extremely promising which on further assessments may provoke medicine particles against Monoamine oxidase A. Especially, C, N can be considered as potent and can be used to treat depression and anxiety.

Monoamine oxidase inhibition by selected dye compounds.

Monoamine oxidase (MAO) is an important drug target as the MAO isoforms play key roles in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, as well as in neuropsychiatric diseases such as depression. Methylene blue is an inhibitor of MAO-A, while azure B, the major metabolite of methylene blue, and various other structural analogues retain the ability to inhibit MAO-A. Based on this, the present study evaluated 22 dyes, many of which are structurally related to methylene blue, as potential inhibitors of human MAO-A and MAO-B. The results highlighted three dye compounds as good potency competitive and reversible MAO inhibitors, and which exhibit higher MAO inhibition than methylene blue: acridine orange, oxazine 170 and Darrow red. Acridine orange was found to be a MAO-A specific inhibitor (IC50 =0.017μM), whereas oxazine 170 is a MAO-B specific inhibitor (IC50 =0.0065μM). Darrow red was found to be a non-specific MAO inhibitor (MAO-A, IC50 =0.059μM; MAO-B, IC50 =0.065μM). These compounds may be advanced for further testing and preclinical development, or be used as possible lead compounds for the future design of MAO inhibitors.

Flavonoids Isolated from Vitex grandifolia, an Underutilized Vegetable, Exert Monoamine A & B Inhibitory and Anti-inflammatory Effects and Their Structure-activity Relationship.

Vitex grandifolia belongs to family Lamiaceae; it consists of flowering plants and it is also called the mint family. The Yoruba people of southwest Nigeria called it "Oriri" or "Efo oriri". This plant is classified as an underutilized vegetable and little is known about its phytochemistry or its biological evaluations. Methanol extracts of the dried leaves and stem of the plant were subjected to fractionation and isolation using vacuum layer and column chromatography methods. The structures of the compounds were elucidated using spectroscopic techniques including IR, 1D-, and 2D-NMR and by comparison with the data reported in the literature. They were evaluated in vitro for the inhibition of monoamine recombinant human MAO-A and -B and anti-inflammatory activities. Three known flavonoids were isolated from the methanolic extract of the leaves of V. grandifolia for the first time to the best of our knowledge, i.e. isoorientin (1), orientin (2), and isovitexin (3). Most of the isolated compounds showed selective inhibition of monoamine oxidase B, inhibition of MAO-B by isoorientin (1) and orientin (2) were 9-fold more potent (IC50 (μg/mL) of 11.08 and 11.04) compared to the inhibition of MAO-A (IC50 (μg/mL) of ˃100), while clorgyline and deprenyl were used as positive standards. The isolated flavonoids displayed good activity against the NF-ﭏb assay with IC50 (μg/mL) of 8.9, 12, and 18. This study establishes a link between the structure and the biological activities on the basis of the different patterns of substitution, particularly the C2=C3 double bond and the position of glucose moiety. This study is the first to establish the phytochemistry of the polar part of V. grandifolia and the anti-inflammatory and neuroprotective role of these isolated compounds.

Novel C7-Substituted Coumarins as Selective Monoamine Oxidase Inhibitors: Discovery, Synthesis and Theoretical Simulation.

There is a continued need to develop new selective human monoamine oxidase (hMAO) inhibitors that could be beneficial for the treatment of neurological diseases. However, hMAOs are closely related with high sequence identity and structural similarity, which hinders the development of selective MAO inhibitors. “Three-Dimensional Biologically Relevant Spectrum (BRS-3D)” method developed by our group has demonstrated its effectiveness in subtype selectivity studies of receptor and enzyme ligands. Here, we report a series of novel C7-substituted coumarins, either synthesized or commercially purchased, which were identified as selective hMAO inhibitors. Most of the compounds demonstrated strong activities with IC50 values (half-inhibitory concentration) ranging from sub-micromolar to nanomolar. Compounds, FR1 and SP1, were identified as the most selective hMAO-A inhibitors, with IC50 values of 1.5 nM (selectivity index (SI) < −2.82) and 19 nM (SI < −2.42), respectively. FR4 and FR5 showed the most potent hMAO-B inhibitory activity, with IC50 of 18 nM and 15 nM (SI > 2.74 and SI > 2.82). Docking calculations and molecular dynamic simulations were performed to elucidate the selectivity preference and SAR profiles.

Attenuation of Ischemic Stroke-Caused Brain Injury by a Monoamine Oxidase Inhibitor Involves Improved Proteostasis and Reduced Neuroinflammation.

Mitochondrial dysfunction and oxidative stress play a key role in ischemia/reperfusion (I/R) induced brain injury. We previously showed that ubiquilin-1 (Ubqln1), a ubiquitin-like protein, improves proteostasis and protects brains against oxidative stress and I/R induced brain injury. We demonstrate here that nialamide (NM), a non-selective monoamine oxidase (MAO) inhibitor, upregulated Ublqn1 and protected neurons from oxygen-glucose deprivation- and I/R-caused cell death in in vitro and in vivo, respectively. Post-ischemic administration of the NM in a stroke mouse model even at 3h following I/R still reduced neuronal injury and improved functional recovery and survival. Treating stroke animals with NM also increased the association of Ubqln1 with mitochondria and decreased the total oxidized and polyubiquitinated protein levels. Intriguingly, NM-enhanced proteostasis was also associated with reduced I/R-caused neuroinflammation, as reflected by attenuated activation of microglia and astrocytes as well as reduced TNF-α level. Thus, our results suggest that MAO inhibition-induced neuroprotection following I/R involves improved proteostasis and reduced neuroinflammation.

Oral Phenelzine Treatment Mitigates Metabolic Disturbances in Mice Fed a High-Fat Diet.

Novel mechanisms and health benefits have been recently suggested for the antidepressant drug phenelzine (PHE), known as a nonselective monoamine oxidase inhibitor. They include an antilipogenic action that could have an impact on excessive fat accumulation and obesity-related metabolic alterations. We evaluated the metabolic effects of an oral PHE treatment on mice fed a high-fat diet (HFD). Eleven-week-old male C57BL/6 mice were fed a HFD and either a 0.028% PHE solution (HFD + PHE) or water to drink for 11 weeks. PHE attenuated the increase in body weight and adiposity without affecting food consumption. Energy efficiency was lower in HFD + PHE mice. Lipid content was reduced in subcutaneous fat pads, liver, and skeletal muscle. In white adipose tissue (WAT), PHE reduced sterol regulatory element-binding protein-1c and phosphoenolpyruvate carboxykinase mRNA levels, inhibited amine-induced lipogenesis, and did not increase lipolysis. Moreover, HFD + PHE mice presented diminished levels of hydrogen peroxide release in subcutaneous WAT and reduced expression of leukocyte transmigration markers and proinflammatory cytokines in visceral WAT and liver. PHE reduced the circulating levels of glycerol, triacylglycerols, high-density lipoprotein cholesterol, and insulin. Insulin resistance was reduced, without affecting glucose levels and glucose tolerance. In contrast, PHE increased rectal temperature and slightly increased energy expenditure. The mitigation of HFD-induced metabolic disturbances points toward a promising role for PHE in obesity treatment and encourages further research on its mechanisms of action. SIGNIFICANCE STATEMENT: Phenelzine reduces body fat, markers of oxidative stress, inflammation, and insulin resistance in high-fat diet mice. Semicarbazide-sensitive amine oxidase, monoamine oxidase, phosphoenolpyruvate carboxykinase, and sterol regulatory element-binding protein-1c are involved in the metabolic effects of phenelzine. Phenelzine could be potentially used for the treatment of obesity-related complications.

Antidepressants Reduced Risk of Mortality in Patients With Diabetes Mellitus: A Population-Based Cohort Study in Taiwan.

The effect of antidepressant (ATD) use on mortality in patients with diabetes mellitus (DM) has not yet been sufficiently studied, although comorbid depression is common in this population. To explore the impact of ATDs on mortality among DM patients. A retrospective cohort study in a national database. This population-based study used the National Health Insurance Research Database in Taiwan. Since 2000, we identified 53,412 cases of newly diagnosed patients with DM and depression. Patient cases were followed for assessing mortality until 2013. The association between mortality and ATD use was explored adjusting for cumulative dosing. Using the time-dependent Cox regression model, ATD use was associated with significantly reduced mortality among patients with DM [in the highest dose group: hazard ratio (HR), 0.65; 95% CI, 0.59 to 0.71]. Further analysis showed that differences in mortality existed across ATD categories: selective serotonin reuptake inhibitors (HR, 0.63; 95% CI, 0.56 to 0.71), serotonin-norepinephrine reuptake inhibitors (HR, 0.58; 95% CI, 0.44 to 0.78), norepinephrine-dopamine reuptake inhibitors (HR, 0.20; 95% CI, 0.07 to 0.63), mirtazapine (HR, 0.60; 95% CI, 0.45 to 0.82), tricyclic/tetracyclic antidepressants (HR, 0.73; 95% CI, 0.54 to 0.97), and trazodone (HR, 0.52; 95% CI, 0.29 to 0.91). However, reversible inhibitor of monoamine oxidase A (RIMA) was found to be associated with an increase, rather than a decrease, in total mortality (HR, 1.48; 95% CI, 1.09 to 1.99). Most ATDs, but not RIMA, were associated with significantly reduced mortality among a population with comorbid DM and depression.

LC-MS/MS method for quantification of 3,4-dihydroxyphenylglycol, a norepinephrine metabolite in plasma and brain regions.

Aim: To evaluate suitability of the LC-MS/MS method to quantify 3,4-dihydroxyphenylglycol (DHPG) that is used as a biomarker for monoamine oxidase (MAO) inhibition. Methods: DHPG was extracted using alumina basic cartridges and quantified on a triple quadrupole mass spectrometer using negative electrospray ionization, without the use of derivatization reagents. Results: Modulation of DHPG levels was observed following administration of selective and nonselective MAO inhibitors and results were in correlation with historical MAO inhibition potential of compounds. Conclusion: The proposed method is sensitive enough to measure plasma DHPG levels and DHPG can be used as a biomarker to assess MAO inhibition potential of new therapeutic agents.

DEPRESSION - TYPES AND TREATMENT OF DEPRESSION

The key symptom of depression is lowering the mood, but this is not the only sign of depression. Depression is a disease in which the symptoms reach various intensities and occur in many configurations. We distinguish the following types of depression: reactive, endogenous, neurotic, anankastic, agitated, large and small, morning (subclinical and subliminal), seasonal, masked, psychotic, postpartum, drug resistant, in children and adolescents, in the elderly, involutional, organic , in bipolar disorder, dysthymia, depression and anxiety, and in somatic diseases. Psychotherapy is now a popular and effective method of treating depression. The effects of treatment after the use of antidepressants appear only after a few weeks from the beginning of therapy. Old-generation medicines: these are tricyclic antidepressants (TLPDs), inhibitors of neuromediator reuptake and monoamine oxidase enzyme (IMAO) inhibitors. The new generation of drugs is distinguished by selective serotonin reuptake inhibitors (SSRIs), selective serotonin and noradrenaline reuptake inhibitors (SNRIs), four-ring drugs, noradrenaline reuptake inhibitors, selective reversible MAO inhibitors, and drugs with other mechanisms of action. Phototherapy (treatment of light) is currently a widely accepted method of winter depression therapy. Other treatments for depression include electroconvulsive therapy and transcranial magnetic stimulation.

Identification of novel monoamine oxidase selective inhibitors employing a hierarchical ligand-based virtual screening strategy.

Aim: Due to the pivotal role in the oxidative deamination of monoamine neurotransmitters, two distinct monoamine oxidase (MAO) subtypes, MAO-A and MAO-B, present a significant pharmacological interest. Here, we reported a hierarchical and time-efficient ligand-based virtual screening strategy to identify potent selective and reversible MAO inhibitors. Result: A total of 130 compounds were assessed in dose-response biochemical assay against MAOs. Among them, 70 compounds were active with inhibition higher than 70%, involving 25 compounds with IC50 values less than 1μM. Conclusion: Our research demonstrated the validity of Biologically Relevant Spectrum (BRS-3D) in predicting subtype-selective ligands and afforded a novel highly efficient way to develop selective inhibitors in the early stage of drug discovery.

Synthesis, X-ray crystal and monoamine oxidase inhibitory activity of 4,6-dihydrobenzo[c]pyrano[2,3-e][1,2]thiazine 5,5-dioxides: In vitro studies and docking analysis

We report the synthesis and biological evaluation of two new series of 2-amino-6-benzyl-4-phenyl-4,6-dihydrobenzo[c]pyrano[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxides and 2-amino-6-methyl-4-phenyl-4,6-dihydrobenzo[c]pyrano[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxides. The synthetic methodology involves a multistep reaction starting with methyl anthranilate which was coupled with methane sulfonyl chloride. The product of the reaction was subjected to N-benzylation and N-methylation reactions followed by ring closure with sodium hydride resulting in the formation of respective 2,1-benzothiazine 2,2-dioxides. These 2,1-benzothiazine precursors were subjected to multicomponent reaction with malononitrile and substituted benzaldehydes for the synthesis of two new series of pyranobenzothiazines (6a–r and 7a–r). The synthesized compounds were screened as selective inhibitors of monoamine oxidase A and monoamine oxidase B. The in vitro results suggested that compound 6d and 7q are the selective inhibitors of monoamine oxidase A, however, the selective and potent inhibitors of monoamine oxidase B included compounds 6h and 7r. Moreover, some dual inhibitors were noticed like 7l having more inhibitory activity towards both the isozymes. Moreover, the binding modes of the selective and potent inhibitors of monoamine oxidase A and B were investigated by molecular docking analysis. The results suggested that the synthetic derivatives may be potential towards the monoamine oxidase isozymes.

Quercetin and Related Chromenone Derivatives as Monoamine Oxidase Inhibitors: Targeting Neurological and Mental Disorders

Monoamine oxidase inhibitions are considered as important targets for the treatment of depression, anxiety, and neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. This has encouraged many medicinal chemistry research groups for the development of most promising selective monoamine oxidase (MAO) inhibitors. A large number of plant isolates also reported for significant MAO inhibition potential in recent years. Differently substituted flavonoids have been prepared and investigated as MAO-A and MAO-B inhibitors. Flavonoid scaffold showed notable antidepressant and neuroprotective properties as revealed by various and established preclinical trials. The current review made an attempt to summarizing and critically evaluating the new findings on the quercetin and related flavonoid derivatives functions as potent MAO isoform inhibitors.

Osthenol, a prenylated coumarin, as a monoamine oxidase A inhibitor with high selectivity

Osthenol (6), a prenylated coumarin isolated from the dried roots of Angelica pubescens, potently and selectively inhibited recombinant human monoamine oxidase-A (hMAO-A) with an IC50 value of 0.74 µM and showed a high selectivity index (SI > 81.1) for hMAO-A versus hMAO-B. Compound 6 was a reversible competitive hMAO-A inhibitor (Ki = 0.26 µM) with a potency greater than toloxatone (IC50 = 0.93 µM), a marketed drug. Isopsoralen (3) and bakuchicin (1), furanocoumarin derivatives isolated from Psoralea corylifolia L., showed slightly higher IC50 values (0.88 and 1.78 µM, respectively) for hMAO-A than 6, but had low SI values (3.1 for both). Other coumarins tested did not effectively inhibit hMAO-A or hMAO-B. A structural comparison suggested that the 8-(3,3-dimethylallyl) group of 6 increased its inhibitory activity against hMAO-A compared with the 6-methoxy group of scopoletin (4). Molecular docking simulations revealed that the binding affinity of 6 for hMAO-A (−8.5 kcal/mol) was greater than that for hMAO-B (−5.6 kcal/mol) and that of 4 for hMAO-A (−7.3 kcal/mol). Docking simulations also implied that 6 interacted with hMAO-A at Phe208 and with hMAO-B at Ile199 by carbon hydrogen bondings. Our findings suggest that osthenol, derived from natural products, is a selective and potent reversible inhibitor of MAO-A, and can be regarded a potential lead compound for the design of novel reversible MAO-A inhibitors.

Monoamine oxidase-B inhibitors as potential neurotherapeutic agents: An overview and update.

Monoamine oxidase (MAO) inhibitors have made significant contributions and remain an indispensable approach of molecular and mechanistic diversity for the discovery of antineurodegenerative drugs. However, their usage has been hampered by nonselective and/or irreversible action which resulted in drawbacks like liver toxicity, cheese effect, and so forth. Hence, the search for selective MAO inhibitors (MAOIs) has become a substantial focus in current drug discovery. This review summarizes our current understanding on MAO-A/MAO-B including their structure, catalytic mechanism, and biological functions with emphases on the role of MAO-B as a potential therapeutic target for the development of medications treating neurodegenerative disorders. It also highlights the recent developments in the discovery of potential MAO-B inhibitors (MAO-BIs) belonging to diverse chemical scaffolds, arising from intensive chemical-mechanistic and computational studies documented during past 3 years (2015-2018), with emphases on their potency and selectivity. Importantly, readers will gain knowledge of various newly established MAO-BI scaffolds and their development potentials. The comprehensive information provided herein will hopefully accelerate ideas for designing novel selective MAO-BIs with superior activity profiles and critical discussions will inflict more caution in the decision-making process in the MAOIs discovery.

Isolation and Identification of Phenylethanoid Glycosides from Aloysia polystachya and Its Activity as Inhibitors of Monoamine Oxidase-A

Abstract Aloysia polystachya is used as a sedative and antidepressant by the indigenous populations of Argentina and Paraguay, but the compounds associated with these activities have not been determined. We have separated and identified the main constituents of the hydroethanolic extract of A. polystachya by ultra-performance liquid chromatography-mass spectrometry and confirmed the presence of acteoside, isoacteoside, 6'-acetylacteoside, and 4’,4’’’,5,5’’-tetrahydroxy-6,6’’,3’’’-trimethoxy-[C7–O–C7’’]-biflavone by NMR spectroscopy. Inhibitory activities of the hydroethanolic extract and purified phenylethanoid glycosides against monoamine oxidase-A were assessed using a standard fluorometric assay. The hydroethanolic extract inhibited monoamine oxidase-A activity in a dose-dependent manner with an IC50 of 9.2 µg/mL, while the selective monoamine oxidase inhibitor clorgyline exhibited an IC50 of 0.06 µg/mL (0.22 µM). Acteoside was the strongest inhibitor of monoamine oxidase-A (IC50 value of 5 µM), whereas isoacteoside and 6'-acetylacteoside showed IC50 values of around 10 µM. The results showed that phenylethanoids from a hydroethanolic extract of A. polystachya have been found to have inhibitory activity against monoamine oxidase-A. It is likely that the mode of action of the acteosides is multi-targeted, involving the downregulation of inflammatory molecules and neutralization of oxidation reactions as well as inhibition of monoamine oxidase-A.

Top New Drug Approvals of 2018

Top New Drug Approvals of 2018

Absolute configuration and biological profile of pyrazoline enantiomers as MAO inhibitory activity.

A new racemic pyrazoline derivative was synthesized and resolved to its enantiomers using analytic and semipreparative high-pressure liquid chromatography. The absolute configuration of both fractions was established using vibrational circular dichroism. The in vitro monoamine oxidase (MAO) inhibitory profiles were evaluated for the racemate and both enantiomers separately for the two isoforms of the enzyme. The racemic compound and both enantiomers were found to inhibit hMAO-A selectively and competitively. In particular, the R enantiomer was detected as an exceptionally potent and a selective MAO-A inhibitor (Ki =0.85×10-3 ±0.05×10-3 μM and SI: 2.35×10-5 ), whereas S was determined as poorer compound than R in terms of Ki and SI (0.184±0.007 and 0.001). The selectivity of the enantiomers was explained by molecular modeling docking studies based on the PDB enzymatic models of MAO isoforms.

Design, synthesis and evaluation of pentacycloundecane and hexacycloundecane propargylamine derivatives as multifunctional neuroprotective agents

The multifactorial pathophysiology of neurodegenerative disorders remains one of the main challenges in the design of a single molecule that may ultimately prevent the progression of these disorders in affected patients. In this article, we report on twelve novel polycyclic amine cage derivatives, synthesized with or without a propargylamine function, designed to possess inherent multifunctional neuroprotective activity. The MTT cytotoxicity assay results showed the SH-SY5Y human neuroblastoma cells to be viable with the twelve compounds, particularly at concentrations less than 10 μM. The compounds also showed significant neuroprotective activity, ranging from 31% to 61% at 1 μM, when assayed on SH-SY5Y human neuroblastoma cells in which neurodegeneration was induced by MPP+. Calcium regulation assays conducted on the same cell line showed the compounds to be significant VGCC blockers with activity ranging from 26.6% to 51.3% at 10 μM; as well as significant NMDAr antagonists with compound 5 showing the best activity of 88.3% at 10 μM. When assayed on human MAO isoenzymes, most of the compounds showed significant inhibitory activity, with compound 5 showing the best activity (MAO-B: IC50 = 1.70 μM). Generally, the compounds were about 3–52 times more selective to the MAO-B isoenzyme than the MAO-A isoenzyme. Based on the time-dependency studies conducted, the compounds can be defined as reversible MAO inhibitors. Several structure activity relationships were derived from the various assays conducted, and the compounds' possible putative binding modes within the MAO-B enzyme cavity were assessed in silico.

Rhamnocitrin isolated from Prunus padus var. seoulensis: A potent and selective reversible inhibitor of human monoamine oxidase A

Three flavanones and two flavones were isolated from the leaves of Prunus padus var. seoulensis by the activity-guided screening for new monoamine oxidase (MAO) inhibitors. Among the compounds isolated, rhamnocitrin (5) was found to potently and selectively inhibit human MAO-A (hMAO-A, IC50 = 0.051 µM) and effectively inhibit hMAO-B (IC50 = 2.97 µM). The IC50 value of 5 for hMAO-A was the lowest amongst all natural flavonoids reported to date, and the potency was 20.2 times higher than that of toloxatone (1.03 µM), a marketed drug. In addition, 5 reversibly and competitively inhibited hMAO-A and hMAO-B with Ki values of 0.030 and 0.91 µM, respectively. Genkwanin (4) was also observed to strongly inhibit hMAO-A and hMAO-B (IC50 = 0.14 and 0.35 µM, respectively), and competitively inhibit hMAO-A and hMAO-B (Ki = 0.097 and 0.12 µM, respectively). Molecular docking simulation reveals that the binding affinity of 5 with hMAO-A (−18.49 kcal/mol) is higher than that observed with hMAO-B (0.19 kcal/mol). Compound 5 interacts with hMAO-A at four possible residues (Asn181, Gln215, Thr336, and Tyr444), while hMAO-B forms a single hydrogen bond at Glu84. These findings suggest that compound 5 as well as 4 can be considered as novel potent and reversible hMAO-A and/or hMAO-B inhibitors or useful lead compounds for future development of hMAO inhibitors in neurological disorder therapies.