Monoamine Oxidase Inhibitory Activity: Methyl‐ versus Chlorochalcone Derivatives

Mathew, Bijo; Uçar, Gülberk; Mathew, Githa Elizabeth; Mathew, Sincy; Purapurath, Praseedha Kalatharakkal; Moolayil, Fasil; Mohan, Smrithy; Gupta, Sheeba Varghese

doi:10.1002/cmdc.201600497

Cited by 54 publications

(31 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The presence of hydroxy and methoxy groups or two hydroxy groups on the ortho and para position of the A aromatic moiety as well as a chlorine atom on the para position of the B ring of chalcones leads to potent MAO−B inhibitory action . Recent studies of our group demonstrated that substitution with chloro or methyl groups on the para substitution of phenyl A system shown potent and reversible type of hMAO−B inhibitors . It is clear that introduction of lipophilic‐electron withdrawing groups such as bromine, chlorine, fluorine and trifluromethyl group on the para position of ring B of chalcones increase the MAO−B inhibitory action.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Thienylchalcones as hMAO‐B Inhibitors: Synthesis, Biochemistry and Molecular Dynamics Studies

et al. 2017

Self Cite

View full text Add to dashboard Cite

The design of selective, reversible and non‐toxic hMAO−B inhibitors has received increasing attention due to their perceived utility in targeting of neurological disorders like Alzheimer's and Parkinson's diseases. For this purpose, herein, we report the inhibitory studies on monoamine oxidase of a series of (2E)‐1‐(2, 5‐dichlorothiophen‐3‐yl)‐3‐(4‐substitutedphenyl) prop‐2‐en‐1‐ones (S1‐S9). All the compounds were found to be competitive, selective, and reversible inhibitors of hMAO−B except (2E)‐1‐(2, 4‐dichlorothiophen‐3‐yl)‐3‐(4‐nitrophenyl) prop‐2‐en‐1‐one (S6) which is found to be non‐selective MAO inhibitor. The potent hMAO−B inhibitor, (2E)‐1‐(2, 4‐dichlorothiophen‐3‐yl)‐3‐[4‐(dimethylamino) phenyl] prop‐2‐en‐1‐one (S4), showed a Ki value of 0.041 μM better than the standard drug, selegiline (hMAO−B with Ki= 0.302 μM). Moreover, S4, was nontoxic in cultured hepatic cells at 5 and 25 μM, with 94.44 and 88.00% viable cells, respectively. Molecular docking and molecular dynamics simulation studies were carried out using Autodock‐vina and Amber 14 to understand the molecular level interaction and energy relation of MAO isoforms with selective MAO−B inhibitor, S4.

show abstract

Section: Introductionmentioning

confidence: 99%

Characterization of Thienylchalcones as hMAO‐B Inhibitors: Synthesis, Biochemistry and Molecular Dynamics Studies

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…This paper investigates the response of voids in reinforced concrete beams. The voided sections were located below the neutral axis as it is more effective [7]. Polystyrene was used as the void former due to its lightweight properties.…”

Section: Introductionmentioning

confidence: 99%

Flexural Behaviour of Reinforced Concrete Beam Embedded with Different Alignment of Polystyrene

2020

BJoST

View full text Add to dashboard Cite

This study investigates the flexural behaviour of reinforced concrete beam embedded with different alignments of polystyrene blocks. Understanding of its behavior would improve beam by maximising reduction of dead load due to concrete volume. Three beams of dimension 1600 mm x 175 mm x 300 mm were tested under the four-point load setup. These specimen had three different alignments of polystyrene block located below the neutral axis. The first specimen with a singular rectangle polystyrene block was used as a reference specimen to investigate the presence of spacing between the polystyrene blocks, and the presence of a mid-span spacing with concrete strut at the sides of the beam. The beams failed due to crushing of concrete at the top with major flexural cracks. The result from the test showed the effects of the alignments of the polystyrene blocks on the beam. The presence of spacings decreases the ultimate capacity per unit volume while increases its ductility. The presence of mid-span spacing and concrete struts improves the ultimate capacity per unit volume but decreases its ductility. Further studies may involve width of the spacings and layout of polystyrene blocks.

show abstract

“…These efforts are mainly focused for the development of MAO‐B inhibitors rather than MAO‐A . It has largely been reported that the presence of electron donating or lipophilic groups such as methyl, dimethylamino, ethyl, bromine, fluorine, and trifluoromethyl groups at ring B of chalcones are favorable for MAO‐B inhibitory activity . Simultaneously, the effect of heterocyclic systems such as thiophene, indole, furan, and imidazole in ring A also produced promising MAO‐B inhibitory potencies by maintaining the above‐mentioned pharmacophore on ring B .…”

Section: Introductionmentioning

confidence: 99%

Potent and highly selective dual‐targeting monoamine oxidase‐B inhibitors: Fluorinated chalcones of morpholine versus imidazole

Mathew

Baek

Parambi

et al. 2019

Archiv der Pharmazie

Self Cite

View full text Add to dashboard Cite

Two series of fluorinated chalcones containing morpholine and imidazole-based compounds (f1-f8) were synthesized and evaluated for recombinant human monoamine oxidase (MAO)-A and -B as well as acetylcholinesterase inhibitory activities.Our results indicate that morpholine containing chalcones are highly selective MAO-B inhibitors having reversibility properties. All the imidazole-based fluorinated chalcones showed weak MAO inhibitions in both isoforms. Among the tested compounds, (2E)-3-(3-fluorophenyl)-1- [4-(morpholin-4-yl)phenyl]prop-2-en-1-one (f2) showed potent inhibitory activity for recombinant human MAO-B (IC 50 = 0.087 μM) with a high selectivity index (SI) of 517.2. In the recovery experiments using dialysis, the residual activity of MAO-B inhibited by f2 was close to that with the reversible reference inhibitor. Inhibition assays revealed that the K i values of f1 and f2 for MAO-B were 0.027 and 0.020 μM, respectively, with competitive patterns. All the morpholine-based compounds (f1-f4) showed moderate inhibition toward acetylcholinesterase with IC 50 values ranging between 24 and 54 μM. All morpholine-containing compounds exhibit good blood-brain barrier permeation in the PAMPA method. The rational approach regarding the highly selective MAO-B inhibitor f2 was further ascertained by induced fit docking and molecular dynamics simulation studies. K E Y W O R D S acetylcholinesterase, chalcone, entrance cavity, imidazole, MAO-B selective inhibitor, molecular dynamics, morpholine Parkinson's disease (PD) encompasses a multicentric progressive loss of specific neuronal cell populations resulting in the development of the movement disorder. PD is the second most prevalent age-related neurodegenerative disease that results from the loss of nigrostriatal dopaminergic neurons. [1] The neurodegeneration is initiated decades before it affects the motor function, and the phenotype is usually characterized by resting tremors, rigidity, and bradykinesia. [2] Monoamine oxidase (MAO; EC 1.4.3.4) has increased expression levels in neuronal tissues as well as gastro and hepatic tissues. [3] MAO-A and MAO-B inhibitors are in clinical use for the treatment of neurological and psychiatric disorders, respectively. [4] Biochemically, these two isoenzymes are differentiated by their substrate and inhibitor specificities. [5] Inhibition of isoform B, which is mainly localized in the raphe nucleus of serotonergic neuronal cell bodies, leads to elevated levels of dopamine (DA) in Parkinsonism patients. The phenomenal advances in neurochemistry have greatly helped in unfolding the pathophysiology of this disorder and provided the basis for the introduction of levodopa. The new understanding and disclosure of the mechanisms of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) in primate models has triggered a resurgence concerning the etiological factors that enhance the inhibition of MAO-B with deprenyl, the first MAO-B inhibitor which potentiates the effects of levodopa and prolongs the life of PD patients. [6]Most MAO-B inh...

show abstract

Monoamine Oxidase Inhibitory Activity: Methyl‐ versus Chlorochalcone Derivatives

Cited by 54 publications

References 51 publications

Characterization of Thienylchalcones as hMAO‐B Inhibitors: Synthesis, Biochemistry and Molecular Dynamics Studies

Characterization of Thienylchalcones as hMAO‐B Inhibitors: Synthesis, Biochemistry and Molecular Dynamics Studies

Flexural Behaviour of Reinforced Concrete Beam Embedded with Different Alignment of Polystyrene

Potent and highly selective dual‐targeting monoamine oxidase‐B inhibitors: Fluorinated chalcones of morpholine versus imidazole

Contact Info

Product

Resources

About