Synthesis and evaluation of 2-substituted 4(3H)-quinazolinone thioether derivatives as monoamine oxidase inhibitors

Qhobosheane, Malikotsi A.; Petzer, Anél; Petzer, Jacobus P.; Legoabe, Lesetja J.

doi:10.1016/j.bmc.2018.09.032

Cited by 25 publications

(12 citation statements)

References 28 publications

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“…Qhobosheane et al reported seven quinazolinone compounds (IC50 < 1 μM) ascertained as potent and specific MAO-B inhibitors, among them the most potent inhibitor, 2-[(3-iodobenzyl)thio]quinazolin-4(3H)-one (128; Figure 17), with IC50 value of 0.142 μM. Although these derivatives have been proved as reversible and competitive MAO-B inhibitor (Ki = 0.068 μM), none of the them were MAO-A inhibitors [106]. Khattab et al [107] reported a series of quinazolinone bearing amino acid ester or amino acid hydrazides (129-131; Figure 17) that revealed competitive higher inhibitory activity toward MAO-A than MAO-B.…”

Section: Monoamine Oxidase Inhibitor Activity (Mao)mentioning

confidence: 99%

Biological Activity of Quinazolinones

Radwan¹,

Alanazi²

2020

Quinazolinone and Quinazoline Derivatives

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The chemical structure of quinazolinones includes benzene ring fused with 2-pyrimidinone (1), 4-pyrimidinone (2) or 2,4-pyrimidinedione (3) ring, and are named as quinazolin-2(1H)-one, quinazolin-4(3H)-one or quinazolin-2,4(1H, 3H)-one, respectively. The chemical structure of quinazolinones constitutes a crucial scaffold of natural and synthetic compounds with various therapeutic and biological activities. Quinazolinones are first synthesized by Stefan Niementowski (1866-1925) and named after Niementowski quinazolinone synthesis. Quinazolinones have strongly attracted the interest of medicinal chemist as they constitute a large class of compounds that exhibited broad spectrum of biological activities including antimicrobial, antimalarial, anticonvulsant, anticancer, antileishmanial, anti-inflammatory, etc. This chapter provides a brief overview on the recent advances on chemical and pharmacological aspects of quinazolinone derivatives published in the last decade.

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Section: Monoamine Oxidase Inhibitor Activity (Mao)mentioning

confidence: 99%

Biological Activity of Quinazolinones

Radwan¹,

Alanazi²

2020

Quinazolinone and Quinazoline Derivatives

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“…13 C NMR spectra were recorded at 125.7 and 75.5 MHz with internal references from solvent carbon signals ( = 77.1 for CDCl 3 and  = 39.5 for DMSO-d 6 ). 19 F NMR spectra were recorded at 470.5 MHz with no internal reference. Coupling constants are reported in Hz and chemical shifts of signals are given in ppm and standard abbreviations were used for multiplicity assignments.…”

Section: Paper Synthesismentioning

confidence: 99%

“…The importance of thioquinazoline derivatives has increased lately. Potential antibacterial, 10,11 antimicrobial, 12 antiviral, 13 antitumor, [14][15][16][17] bronchodilatory 18 activity, and monoamine oxidase inhibitor activity, 19 which is important for the treatment of Parkinson's disease were found among 2-substituted 4(3H)-quinazoline-4-thiones, substituted 2-thioquinazolin-4-one analogues, and unsubstituted or 2-substituted 4-thioquinazolines. Compounds from the 4-thioquinazoline series are also known as agriculture antimicrobials.…”

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confidence: 99%

Application of Azide-Tetrazole Tautomerism and Arylsulfanyl Group Dance in the Synthesis of Thiosubstituted Tetrazoloquinazolines

et al. 2020

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Nucleophilic aromatic substitution reaction between 4-arylthio-2-chloroquinazolines and NaN3 takes place with an unusual sulfanyl group dance and leads to the formation of 5-(arylthio)tetrazolo[1,5-c]-quinazolines, which do not form the azide tautomer and do not undergo CuAAC reactions with alkynes. On the other hand, 5-azidotetrazolo[1,5-a]quinazoline (formally described as 2,4-diazidoquinazoline) undergoes regioselective nucleophilic aromatic substitution with thiols at C5 and forms 5-(alkyl/arylthio)tetrazolo[1,5-a]quinazolines, the structure of which has been proved by X-ray crystallography. The latter exist in tautomeric equilibrium with their 2-azidoquinazoline form, which provides possibility for copper-catalyzed azide–alkyne 1,3-dipolar cycloaddition reaction, leading to the 4-alkyl/arylthio-2-(1H-1,2,3-triazol-1-yl)quinazolines.

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“…Quinazolinone is a heterocyclic nitrogen containing system composed of fused phenyl and pyrimidinone (pyrimidone) rings. Over the years, natural and synthetic quinazolinones have attracted attention since they display a variety of biological activities [16][17][18][19] including MAO inhibition [20][21][22][23][24]. Other biological activities of quinazolinones include antimicrobial, anticonvulsant, anticancer, antimalarial, antihypertensive, anti-inflammatory, antidiabetic, antitumor, anticholinesterase, dihydrofolate reductase inhibition, as well as the inhibition of cellular phosphorylation and kinases [25].…”

Section: Introductionmentioning

confidence: 99%

The monoamine oxidase inhibition properties of C6- and N1-substituted 3-methyl-3,4-dihydroquinazolin-2(1H)-one derivatives

Marais

Petzer

2019

Mol Divers

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Quinazolinone compounds are of interest in medicinal chemistry since they display a wide range of biological properties. In the present study, a series of C6-and N1-substituted 3-methyl-3,4-dihydroquinazolin-2(1H)-one derivatives were synthesised and evaluated as inhibitors of recombinant human monoamine oxidase (MAO). Some of these quinazolinones are structurally related to a series of 3,4-dihydro-2(1H)-quinolinone derivatives, which have previously been reported to act as specific inhibitors of MAO-B. The results document that, among 37 compounds synthesised, seven displayed IC 50 values < 1 µM for the inhibition of MAO-B. The most potent MAO-A inhibitor exhibits an IC 50 value of 7.43 µM while the most potent MAO-B inhibitor possesses an IC 50 value of 0.269 µM. Good-potency MAO inhibition was only observed among C6-substituted 3-methyl-3,4-dihydroquinazolin-2(1H)-one derivatives with N1-substitution yielding comparatively lowpotency inhibition. MAO-B-specific inhibitors such as some of the quinazolinone compounds investigated here may act as leads for the design of therapies for neurodegenerative disorders such as Parkinson's disease.

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Synthesis and evaluation of 2-substituted 4(3H)-quinazolinone thioether derivatives as monoamine oxidase inhibitors

Cited by 25 publications

References 28 publications

Biological Activity of Quinazolinones

Biological Activity of Quinazolinones

Application of Azide-Tetrazole Tautomerism and Arylsulfanyl Group Dance in the Synthesis of Thiosubstituted Tetrazoloquinazolines

The monoamine oxidase inhibition properties of C6- and N1-substituted 3-methyl-3,4-dihydroquinazolin-2(1H)-one derivatives

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