8-Aryl- and alkyloxycaffeine analogues as inhibitors of monoamine oxidase

Strydom, Belinda; Bergh, Jacobus J.; Petzer, Jacobus P.

doi:10.1016/j.ejmech.2011.05.014

Cited by 31 publications

(20 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The features of this proposed pharmacophore is apparent when considering the architecture of the MAO-B active site that is reported to consist of an entrance cavity which leads to a larger substrate cavity [60]. 5) [64]. This area is occupied by highly conserved water molecules and is also the site where the amine functional group of a substrate is predicted to bind [22].…”

Section: Mao-b Inhibitors As Multifunctional Agentsmentioning

confidence: 96%

Multifunctional Enzyme Inhibition for Neuroprotection - A Focus on MAO, NOS, and AChE Inhibitors

Joubert

Petzer

Prins

et al. 2014

Drug Design and Discovery in Alzheimer's Disease

Self Cite

View full text Add to dashboard Cite

Section: Mao-b Inhibitors As Multifunctional Agentsmentioning

confidence: 96%

Multifunctional Enzyme Inhibition for Neuroprotection - A Focus on MAO, NOS, and AChE Inhibitors

Joubert

Petzer

Prins

et al. 2014

Drug Design and Discovery in Alzheimer's Disease

Self Cite

View full text Add to dashboard Cite

“…Another C8 oxy substituent that leads to potent MAO-B inhibition is the 2-phenoxyethoxy moiety. In fact, 8-(2-phenoxyethoxy)caff eine ( 3a ) (IC 50 = 0.383 μM) is a more potent inhibitor of human MAO-B than is 8-benzyloxycaff eine (IC 50 = 1.77 μM) [ 14 ] . A structureactivity relationship (SAR) study has indicated that for C8-substituted oxycaff eine analogues, a linker consisting of 4 atoms separating the caff eine and the terminal phenyl ring may be particularly suited for MAO-B inhibition [ 14 ] .…”

Section: The Inhibition Of Monoamine Oxidase By 8-(2-phenoxyethoxy)camentioning

confidence: 99%

“…In fact, 8-(2-phenoxyethoxy)caff eine ( 3a ) (IC 50 = 0.383 μM) is a more potent inhibitor of human MAO-B than is 8-benzyloxycaff eine (IC 50 = 1.77 μM) [ 14 ] . A structureactivity relationship (SAR) study has indicated that for C8-substituted oxycaff eine analogues, a linker consisting of 4 atoms separating the caff eine and the terminal phenyl ring may be particularly suited for MAO-B inhibition [ 14 ] . Since this requirement is satisfi ed by the 8-(2-phenoxyethoxy)caff eine structure, this compound may be considered to be a promising lead compound for the design of highly potent MAO-B inhibitors.…”

Section: The Inhibition Of Monoamine Oxidase By 8-(2-phenoxyethoxy)camentioning

confidence: 99%

“…The reaction was cooled to room temperature and the 8-(2-phenoxyethoxy)caff eine analogue was recrystallized (at 4 °C) after the addition of ethanol (10-20 mL) to the reaction mixture. The melting points and structure characterizations of compounds 3a -c have been previously reported [ 14 ] . The physical data of 3d are cited below.…”

Section: Procedures For the Synthesis Of The 8-(2-phenoxyethoxy)caff mentioning

confidence: 99%

See 1 more Smart Citation

The Inhibition of Monoamine Oxidase by 8-(2-Phenoxyethoxy)Caffeine Analogues

Strydom

Bergh

Petzer

2012

Arzneimittelforschung

View full text Add to dashboard Cite

Previous studies have documented that substituted 8-oxycaffeines act as inhibitors of human monoamine oxidase (MAO) B. A particularly potent inhibitor among the reported compounds was 8-(2-phenoxyethoxy)caffeine with an IC50 value of 0.383 µM towards MAO-B. In an attempt to improve on the inhibition potency of this compound and to discover highly potent reversible MAO-B inhibitors, in the present study, a series of 8-(2-phenoxyethoxy)caffeine analogues containing various substituents on C4 of the phenoxy ring, were synthesized and evaluated as inhibitors of human MAO-A and -B. The results show that the 8-(2-phenoxyethoxy)caffeine analogues are selective and reversible MAO-B inhibitors with the most potent homologue, 8-{2-[4-(trifluoromethyl)phenoxy]ethoxy}caffeine, exhibiting an IC50 value of 0.061 μM. These highly potent inhibitors are useful leads in the design of therapies for neurodegenerative disorders such as Parkinson's disease.

show abstract

“…Caffeine is a weak inhibitor of MAOs. However, it has been described that substitution at C8 of caffeine with alkyloxy substituents yielded particularly potent MAO−B inhibitors . These derivatives are also MAO−A inhibitors, probably due to the relatively large degree of rotational freedom of the C8 side chain at the C−O ether bond …”

Section: Introductionmentioning

confidence: 99%

Anodic Oxidation of Caffeine and Theophylline in Glacial Acetic Acid

et al. 2016

View full text Add to dashboard Cite

The anodic oxidation of caffeine and theophylline has been carried out at a controlled potential in a one compartment cell using glassy-carbon as the anode, platinum as the cathode and glacial acetic acid/sodium acetate as solvent-supporting-electrolyte (SSE). The oxidation of caffeine yields 1, 3,8-trimethyl-1,3,6,8-tetrazaspiro[4.4]nonane-2,4,7,9-tetrone and (4-acetoxy-1,3,7-trimethyl-2,6,8-trioxo-9H-purin-5-yl) acetate. Despite of the different structure, the oxidation of theophylline leads only to the same spiro compound 1, 3,8-trimethyl-1,3,6,8-tetrazaspiro [4.4]nonane-2,4,7,9-tetrone as in the case of caffeine. The structure of both compounds is described and the reaction mechanism is discussed.

show abstract

8-Aryl- and alkyloxycaffeine analogues as inhibitors of monoamine oxidase

Cited by 31 publications

References 43 publications

Multifunctional Enzyme Inhibition for Neuroprotection - A Focus on MAO, NOS, and AChE Inhibitors

Multifunctional Enzyme Inhibition for Neuroprotection - A Focus on MAO, NOS, and AChE Inhibitors

The Inhibition of Monoamine Oxidase by 8-(2-Phenoxyethoxy)Caffeine Analogues

Anodic Oxidation of Caffeine and Theophylline in Glacial Acetic Acid

Contact Info

Product

Resources

About