scholarly journals Synthesis of N′-(4-/3-/2-/Non-substituted benzylidene)-4-[(4-methylphenyl)sulfonyloxy] Benzohydrazides and Evaluation of Their Inhibitory Activities against Monoamine Oxidases and β-Secretase

2021 ◽  
Vol 11 (13) ◽  
pp. 5830
Author(s):  
Hasan Erdinç Sellitepe ◽  
Jong Min Oh ◽  
İnci Selin Doğan ◽  
Sercan Yildirim ◽  
Ahmet Buğra Aksel ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Potent Inhibitor ◽  
Residual Activity ◽  
Docking Studies ◽  
Monoamine Oxidases ◽  
Mao B ◽  
Ic50 Value ◽  
Mao A ◽  
Inhibitory Activities ◽  
Bace 1

Nineteen tosylated acyl hydrazone derivatives were synthesized, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE-1) were evaluated. Compound 3o was the most potent inhibitor of MAO-A, with an IC50 value of 1.54 µM, followed by 3a (IC50 = 3.35 µM). A structural comparison with 3a indicated that the 3-F group in 3o increased its inhibitory activity against MAO-A. Compound 3s was the most potent inhibitor of MAO-B, with an IC50 value of 3.64 µM, followed by 3t (IC50 = 5.69 µM). The MAO-B inhibitory activity increased in the order of 3- > 4- > 2-NO2 groups in 3s, 3t, and 3r, respectively. All the compounds weakly inhibited AChE and BChE, which retained >50% residual activity at 10 µM, except for 3a, which inhibited BChE with an IC50 value of 16.1 µM. Interestingly, 3e, 3f, and 3n inhibited BACE-1 with IC50 values of 8.63, 9.92, and 8.47 µM, respectively, which were lower than the IC50 of the quercetin reference. Compounds 3o and 3s were found to be reversible competitive inhibitors of MAO-A and MAO-B, respectively, with Ki values of 0.35 ± 0.074 and 1.97 ± 0.65 µM, respectively. Moreover, compounds 3e, 3f, and 3n were effective BACE-1 inhibitors. The lead molecules were further investigated by molecular docking studies to elucidate the binding interactions with the target enzymes.

scholarly journals Pyrazolobenzothiazine-based carbothioamides as new structural leads for the inhibition of monoamine oxidases: design, synthesis, in vitro bioevaluation and molecular docking studies

MedChemComm ◽  
2017 ◽  
Vol 8 (2) ◽  
pp. 452-464 ◽  
Author(s):  
Syed Mobasher Ali Abid ◽  
Sana Aslam ◽  
Sumera Zaib ◽  
Syeda Mahwish Bakht ◽  
Matloob Ahmad ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Potent Inhibitor ◽  
Binding Mode ◽  
Docking Studies ◽  
Design Synthesis ◽  
Molecular Docking Studies ◽  
Monoamine Oxidases ◽  
Mao B

Binding mode of potent inhibitor (green) & cognate ligand (pink) in the active site of MAO-B.

Synthesis, in vitro Acetylcholinesterase Inhibitory Activity Evaluation and Docking Investigation of Some Aromatic Chalcones

MedPharmRes ◽  
2017 ◽  
Vol 1 (1) ◽  
pp. 15-25
Author(s):  
Dao Tran ◽  
Son Tran ◽  
Vi Nguyen ◽  
Tri Le ◽  
Minh Thai ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Condensation Reaction ◽  
Acetylcholinesterase Inhibitors ◽  
Docking Studies ◽  
Acetylcholinesterase Inhibitory Activity ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Inhibitory Activities ◽  
Ellman’S Method

In this study, a total of twenty chalcones were synthesized via Claisen-Schmidt condensation reaction and evaluated for their in vitro acetylcholinesterase inhibitory activities using Ellman’s method. Molecular docking studies on acetylcholinesterase were performed to elucidate the interactions between these chalcone derivatives and acetylcholinesterase active site at the molecular level. From the series, six compounds (S1-5 and S17) exhibited strong acetylcholinesterase inhibitory activities with IC50 values below 100 µM compared to the parent unsubstituted chalcone. Compound S17 (4’-amino-2-chlorochalcone) showed the strongest acetylcholinesterase inhibitory activity in the investigated group with IC50 value of 36.10 µM. Molecular modeling studies were consistent with the results of in vitro acetylcholinesterase inhibitory activities, and chalcone S17 could be considered as a potential lead compound for the development of new acetylcholinesterase inhibitors.

scholarly journals Development of Halogenated Pyrazolines as Selective Monoamine Oxidase-B Inhibitors: Deciphering via Molecular Dynamics Approach

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3264
Author(s):  
Aathira Sujathan Nair ◽  
Jong-Min Oh ◽  
Vishal Payyalot Koyiparambath ◽  
Sunil Kumar ◽  
Sachithra Thazhathuveedu Sudevan ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Monoamine Oxidase ◽  
Phenyl Ring ◽  
Competitive Inhibitor ◽  
Selectivity Index ◽  
Monoamine Oxidase A ◽  
Mao B ◽  
Ic50 Value ◽  
The Central Nervous System ◽  
Inhibitory Activities

Halogens have been reported to play a major role in the inhibition of monoamine oxidase (MAO), relating to diverse cognitive functions of the central nervous system. Pyrazoline/halogenated pyrazolines were investigated for their inhibitory activities against human monoamine oxidase-A and -B. Halogen substitutions on the phenyl ring located at the fifth position of pyrazoline showed potent MAO-B inhibition. Compound 3-(4-ethoxyphenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole (EH7) showed the highest potency against MAO-B with an IC50 value of 0.063 µM. The potencies against MAO-B were increased in the order of –F (in EH7) > –Cl (EH6) > –Br (EH8) > –H (EH1). The residual activities of most compounds for MAO-A were > 50% at 10 µM, except for EH7 and EH8 (IC50 = 8.38 and 4.31 µM, respectively). EH7 showed the highest selectivity index (SI) value of 133.0 for MAO-B, followed by EH6 at > 55.8. EH7 was a reversible and competitive inhibitor of MAO-B in kinetic and reversibility experiments with a Ki value of 0.034 ± 0.0067 µM. The molecular dynamics study documented that EH7 had a good binding affinity and motional movement within the active site with high stability. It was observed by MM-PBSA that the chirality had little effect on the overall binding of EH7 to MAO-B. Thus, EH7 can be employed for the development of lead molecules for the treatment of various neurodegenerative disorders.

scholarly journals Monoamine Oxidase Inhibitory Activity of Biflavonoids from Branches of Garcinia gardneriana (Clusiaceae)

2017 ◽  
Vol 12 (4) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Maria Angélica Recalde-Gil ◽  
Luiz Carlos Klein-Júnior ◽  
Carolina dos Santos Passos ◽  
Juliana Salton ◽  
Sérgio Augusto de Loreto Bordignon ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Inhibitory Activity ◽  
Ethanol Extract ◽  
Ethyl Acetate Fraction ◽  
Spectrometric Data ◽  
Mao B ◽  
Inhibitory Compounds ◽  
Mao A ◽  
Mao Activity

Garcinia gardneriana is chemically characterized by the presence of biflavonoids. Taking into account that flavonoids are able to inhibit monoamine oxidase (MAO) activity, in the present study, the chemical composition of the branches’ extract of the plant is described for the first time and the MAO inhibitory activity of the isolated biflavonoids was evaluated. Based on spectroscopic and spectrometric data, it was possible to identify volkesiflavone, morelloflavone (1), Gb-2a (2) and Gb-2a-7- O-glucoside (3) in the ethyl acetate fraction from ethanol extract of the branches. Compounds 1-3 were evaluated in vitro and demonstrated the capacity to inhibit MAO-A activity with an IC50 ranging from 5.05 to 10.7 μM, and from 20.7 to 66.2 μM for MAO-B. These inhibitions corroborate with previous IC50 obtained for monomeric flavonoids, with a higher selectivity for MAO-A isoform. The obtained results indicate that biflavonoids might be promising structures for the identification of new MAO inhibitory compounds.

scholarly journals Design, synthesis, molecular modelling and in vitro screening of monoamine oxidase inhibitory activities of novel quinazolyl hydrazine derivatives

2020 ◽  
Vol 7 (4) ◽  
pp. 200050
Author(s):  
Adel Amer ◽  
Abdelrahman H. Hegazi ◽  
Mohammed Khalil Alshekh ◽  
Hany E. A. Ahmed ◽  
Saied M. Soliman ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Monoamine Oxidase ◽  
In Vitro Screening ◽  
Phenyl Substituent ◽  
Design Synthesis ◽  
Mao B ◽  
Mao A ◽  
Ft Ir ◽  
Inhibitory Activities

A new series of N'-substituted benzylidene-2-(4-oxo-2-phenyl-1,4-dihydroquinazolin-3(2H)-yl)acetohydrazide ( 5a–5h ) has been synthesized, characterized by FT-IR, NMR spectroscopy and mass spectrometry and tested against human monoamine oxidase (MAO) A and B. Only (4-hydroxy-3-methoxybenzylidene) substituted compounds gave submicromolar inhibition of MAO-A and MAO-B. Changing the phenyl substituent to methyl on the unsaturated quinazoline ring ( 12a–12d ) decreased inhibition, but a less flexible linker ( 14a–14d ) resulted in selective micromolar inhibition of hMAO-B providing insight for ongoing design.

scholarly journals Multifunctional Monoamine Oxidases and Cholinesterases Inhibitory Effects, as well as UPLC-DAD-MS Chemical Profile of Alkaloid Fractions Obtained from Species of the Palicoureeae Tribe

2016 ◽  
Vol 11 (9) ◽  
pp. 1934578X1601100 ◽  
Author(s):  
Luiz Carlos Klein-Júnior ◽  
Carolina dos Santos Passos ◽  
Juliana Salton ◽  
Fernanda Gobbi Bitencourt de ◽  
Luís Funez ◽  
...  
Keyword(s):  
Indole Alkaloids ◽  
The Other ◽  
Chemical Profile ◽  
Inhibitory Effects ◽  
Pharmacological Activities ◽  
Monoamine Oxidases ◽  
Mao B ◽  
Bche Activity ◽  
Neuropsychiatric Diseases ◽  
Mao A

In the present study, the effects were evaluated of alkaloid fractions (AFs) from Psychotria species and correlated genera, Palicourea and Rudgea, on monoamine oxidases (MAOs) and cholinesterases (ChEs). By HPLC-DAD and UPLC-DAD-MS analyses, indole alkaloids (IA) were detected in all AFs. For the Psychotria and Palicourea species, these IA corresponded to tetrahydro-β-carboline alkaloids (THβCA). On the other hand, pyrrolidinoindoline core compounds were observed for Rudgea species. Regarding their pharmacological activities, none of the AFs was able to inhibit AChE. However, the BChE activity was impaired by the Psychotria and Palicourea AFs. In addition, MAO-A was inhibited by both AFs, but only Psychotria nemorosa AF was able to inhibit significantly MAO-B. Rudgea AFs demonstrated a poor inhibitory profile on MAO-A. Taken together, our results highlighted the Psychotria and Palicourea genera as important sources of scaffolds for the development of MAO-A and BChE inhibitors aiming at the treatment of neurodegenerative and neuropsychiatric diseases.

scholarly journals Inhibition of Butyrylcholinesterase by Glycyrol, a Coumarin, Isolated from Glycyrrhiza Uralensis

2020 ◽  
Author(s):  
Geum Seok Jeong ◽  
Myung-Gyun Kang ◽  
Joon Yeop Lee ◽  
Sang Ryong Lee ◽  
Daeui Park ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Competitive Inhibitor ◽  
Glycyrrhiza Uralensis ◽  
Form Hydrogen Bond ◽  
Docking Simulations ◽  
Mao B ◽  
Mao A ◽  
Ic50 Values ◽  
Noncompetitive Inhibitor ◽  
Inhibitory Activities

Eight compounds were isolated from the roots of Glycyrrhiza uralensis and tested for cholinesterase (ChE) and monoamine oxidase (MAO) inhibitory activities. Glycyrol (GC) effectively inhibited butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) with IC50 values of 7.22 and 14.77 µM, respectively, and also moderately inhibited MAO-B (29.48 µM). Six of the other seven compounds only weakly inhibited AChE and BChE, whereas liquiritin apioside moderately inhibited AChE (IC50 = 36.68 µM). Liquiritigenin (LG) potently inhibited MAO-B (IC50 = 0.098 µM) and MAO-A (IC50 = 0.27 µM), and liquiritin, a glycoside of LG, weakly inhibited MAO-B (> 40 µM). GC was a reversible, noncompetitive inhibitor of BChE with a Ki value of 4.47 µM, and LG was a reversible competitive inhibitor of MAO-B with a Ki value of 0.024 µM. Docking simulations showed that the binding affinity of GC for BChE (-7.8 kcal/mol) was greater than its affinity for AChE (-7.1 kcal/mol), and suggested that GC interacted with BChE at Thr284 and Val288 by hydrogen bonds (distances: 2.42 and 1.92 Å, respectively) beyond the ligand binding site of BChE, but that GC did not form hydrogen bond with AChE. The binding affinity of LG for MAO-B (-8.8 kcal/mol) was greater than its affinity for MAO-A (-7.9 kcal/mol). These findings suggest GC and LG should be considered promising compounds for the treatment of Alzheimer’s disease with multi-targeting activities.

scholarly journals Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6640
Author(s):  
Derya Osmaniye ◽  
Berkant Kurban ◽  
Begüm Nurpelin Sağlık ◽  
Serkan Levent ◽  
Yusuf Özkay ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Active Sites ◽  
Docking Study ◽  
Fluorometric Method ◽  
Mao B ◽  
Micromolar Concentration ◽  
Ic50 Value ◽  
Competitive Inhibitors ◽  
New Compounds

MAO-B inhibitors are frequently used in the treatment of neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Due to the limited number of compounds available in this field, there is a need to develop new compounds. In the recent works, it was shown that various thiosemicarbazone derivatives show hMAO inhibitory activity in the range of micromolar concentration. It is thought that benzofuran and benzothiophene structures may mimic structures such as indane and indanone, which are frequently found in the structures of such inhibitors. Based on this view, new benzofuran/benzothiophene and thiosemicarbazone hybrid compounds were synthesized, characterized and screened for their hMAO-A and hMAO-B inhibitory activity by an in vitro fluorometric method. The compounds including methoxyethyl substituent (2b and 2h) were found to be the most effective agents in the series against MAO-B enzyme with the IC50 value of 0.042 ± 0.002 µM and 0.056 ± 0.002 µM, respectively. The mechanism of hMAO-B inhibition of compounds 2b and 2h was investigated by Lineweaver–Burk graphics. Compounds 2b and 2h were reversible and non-competitive inhibitors with similar inhibition features as the substrates. The Ki values of compounds 2b and 2h were calculated as 0.035 µM and 0.046 µM, respectively, with the help of secondary plots. The docking study of compound 2b and 2h revealed that there is a strong interaction between the active sites of hMAO-B and analyzed compound.

scholarly journals Small Multitarget Molecules Incorporating the Enone Moiety

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 199 ◽  
Author(s):  
Thalia Liargkova ◽  
Nikolaos Eleftheriadis ◽  
Frank Dekker ◽  
Efstathia Voulgari ◽  
Constantinos Avgoustakis ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Ache Activity ◽  
Potent Inhibitor ◽  
Biological Activities ◽  
Aggregation Process ◽  
Acetyl Cholinesterase ◽  
Multifactorial Diseases ◽  
Protective Actions ◽  
Ic50 Value ◽  
Inhibitory Activities

Chalcones represent a class of small drug/druglike molecules with different and multitarget biological activities. Small multi-target drugs have attracted considerable interest in the last decade due their advantages in the treatment of complex and multifactorial diseases, since “one drug-one target” therapies have failed in many cases to demonstrate clinical efficacy. In this context, we designed and synthesized potential new small multi-target agents with lipoxygenase (LOX), acetyl cholinesterase (AChE) and lipid peroxidation inhibitory activities, as well as antioxidant activity based on 2-/4- hydroxy-chalcones and the bis-etherified bis-chalcone skeleton. Furthermore, the synthesized molecules were evaluated for their cytotoxicity. Simple chalcone b4 presents significant inhibitory activity against the 15-human LOX with an IC50 value 9.5 µM, interesting anti-AChE activity, and anti-lipid peroxidation behavior. Bis-etherified chalcone c12 is the most potent inhibitor of AChE within the bis-etherified bis-chalcones followed by c11. Bis-chalcones c11 and c12 were found to combine anti-LOX, anti-AchE, and anti-lipid peroxidation activities. It seems that the anti-lipid peroxidation activity supports the anti-LOX activity for the significantly active bis-chalcones. Our circular dichroism (CD) study identified two structures capable of interfering with the aggregation process of Aβ. Compounds c2 and c4 display additional protective actions against Alzheimer’s disease (AD) and add to the pleiotropic profile of the chalcone derivatives. Predicted results indicate that the majority of the compounds with the exception of c11 (144 Å) can cross the Blood Brain Barrier (BBB) and act in CNS. The results led us to propose new leads and to conclude that the presence of a double enone group supports better biological activities.

scholarly journals Monoamine Oxidases, Oxidative Stress, and Altered Mitochondrial Dynamics in Cardiac Ageing

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Damien Maggiorani ◽  
Nicola Manzella ◽  
Dale E. Edmondson ◽  
Andrea Mattevi ◽  
Angelo Parini ◽  
...  
Keyword(s):  
Mitochondrial Dynamics ◽  
Scientific Evidence ◽  
Mitochondrial Enzymes ◽  
Oxidative Deamination ◽  
Monoamine Oxidases ◽  
Mao B ◽  
The Past ◽  
Age Dependent ◽  
Mao A

The advances in healthcare over the past several decades have resulted in populations now living longer. With this increase in longevity, a wider prevalence of cardiovascular diseases is more common and known to be a major factor in rising healthcare costs. A wealth of scientific evidence has implicated cell senescence as an important component in the etiology of these age-dependent pathologies. A number of studies indicate that an excess of reactive oxygen species (ROS) contributes to trigger and accelerate the cardiac senescence processes, and a new role of monoamine oxidases, MAO-A and MAO-B, is emerging in this context. These mitochondrial enzymes regulate the level of catecholamines and serotonin by catalyzing their oxidative deamination in the heart. MAOs’ expression substantially increases with ageing (6-fold MAO-A in the heart and 4-fold MAO-B in neuronal tissue), and their involvement in cardiac diseases is supposedly related to the formation of ROS, via the hydrogen peroxide produced during the substrate degradation. Here, we will review the most recent advances in this field and describe why MAOs could be effective targets in order to prevent age-associated cardiovascular disease.

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