Asymmetric synthesis, molecular modeling and biological evaluation of 5-methyl-3-aryloxazolidine-2,4-dione enantiomers as monoamine oxidase (MAO) inhibitors

Gunal, Sule Erol; Tuncel, Senel Teke; Kelekçi, Nesrin Gökhan; Uçar, Gülberk; Dursun, Basak Yuce; Erdem, Safiye Sağ; Doğan, İlknur

doi:10.1016/j.bioorg.2018.02.003

Cited by 15 publications

(2 citation statements)

References 48 publications

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“…Befloxatone and toloxatone, N-substituted phenyloxazolidinone derivatives, are reversible inhibitors of monoamine oxidase (MAO) [12,13]. N-Aryloxazolidinedione compounds, which are toloxatone derivatives, have been reported to exhibit good affinity for human MAO-A [14].…”

Section: Introductionmentioning

confidence: 99%

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

Demir¹,

Sarı²,

Çetinkaya³

et al. 2020

Beilstein J. Org. Chem.

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The one-pot reaction of chlorosulfonyl isocyanate (CSI) with epoxides having phenyl, benzyl and fused cyclic alkyl groups in different solvents under mild reaction conditions without additives and catalysts was studied. Oxazolidinones and five-membered cyclic carbonates were obtained in ratios close to 1:1 in the cyclization reactions. The best yields of these compounds were obtained in dichloromethane (DCM). Together with 16 known compounds, two novel oxazolidinone derivatives and two novel cyclic carbonates were synthesized with an efficient and straightforward method. Compared to the existing methods, the synthetic approach presented here provides the following distinct advantageous: being a one-pot reaction with metal-free reagent, having shorter reaction times, good yields and a very simple purification method. Moreover, using the density functional theory (DFT) method at the M06-2X/6-31+G(d,p) level of theory the mechanism of the cycloaddition reactions has been elucidated. The further investigation of the potential energy surfaces associated with two possible channels leading to oxazolidinones and five-membered cyclic carbonates disclosed that the cycloaddition reaction proceeds via an asynchronous concerted mechanism in gas phase and in DCM.

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Section: Introductionmentioning

confidence: 99%

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

Demir¹,

Sarı²,

Çetinkaya³

et al. 2020

Beilstein J. Org. Chem.

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“…However, they were withdrawn due to their toxic side effects . Subsequently, different families of heterocycles containing 2 or 4 nitrogen atoms were used as scaffolds for synthesizing reversible and selective MAO inhibitors . 2‐Pyrazolines, which form one of these families, can also be considered as a cyclic hydrazine derivative.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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.

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Design and synthesis of novel chalcone derivatives and evaluation of their inhibitory activities against acetylcholinesterase

Ceyhun

Karaca

Osmaniye

et al. 2021

Archiv der Pharmazie

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According to the cholinergic hypothesis, an increase in the acetylcholine level in Alzheimer's disease patients relatively slows down the symptoms of the disease. The most commonly used drug, donepezil, is a cholinesterase inhibitor. In this study, 12 new chalcones (2a–l) were designed and synthesized. In biological activity studies, the acetylcholinesterase (AChE) and butyrylcholinesterase inhibitory potentials of all compounds were evaluated using the in vitro Ellman method. The biological evaluation showed that compounds 2d, 2f, 2j, and 2l displayed significant activity against AChE. The compounds 2d, 2f, 2j, and 2l displayed IC50 values of 0.042, 0.024, 0.053, and 0.033 µM against AChE, respectively. The reference drug donepezil (IC50 = 0.021 µM) also displayed significant inhibition of AChE. The inhibitory activities of these compounds for β‐amyloid plaque aggregation were investigated. The enzyme kinetic study was performed to observe the effect of the most active compound 2f on the substrate–enzyme relationship, and a mixed‐type inhibition of AchE was determined. Further, docking simulation also revealed that these compounds (2d, 2f, 2j, and 2l) interacted with the enzyme active site in a similar manner to donepezil. The most active derivative, compound 2f, interacted with the amino acids Trp286, Phe295, Tyr341, Trp86, and Glu202.

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Asymmetric synthesis, molecular modeling and biological evaluation of 5-methyl-3-aryloxazolidine-2,4-dione enantiomers as monoamine oxidase (MAO) inhibitors

Cited by 15 publications

References 48 publications

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

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

Design and synthesis of novel chalcone derivatives and evaluation of their inhibitory activities against acetylcholinesterase

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