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

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

doi:10.1055/s-0032-1323662

Cited by 17 publications

(11 citation statements)

References 18 publications

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“…The dialysis buffer was replaced 3 and 7 hr after the start of dialysis with fresh buffer. As positive controls for MAO‐A and MAO‐B, similar dialysis of the enzymes was carried out in the presence of the irreversible inhibitors, pargyline (IC 50 = 13 μM) and selegiline (IC 50 = 0.079 μM), respectively (Petzer et al, ; Strydom, Bergh, & Petzer, ). Although pargyline was used as a MAO‐A inhibitor, it is non‐specific and also inhibits MAO‐B.…”

Section: Methodsmentioning

confidence: 99%

Monoamine oxidase inhibition by selected dye compounds

Beer

Petzer

2019

Chem Biol Drug Des

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Monoamine oxidase (MAO) is an important drug target as the MAO isoforms play key roles in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, as well as in neuropsychiatric diseases such as depression. Methylene blue is an inhibitor of MAO‐A, while azure B, the major metabolite of methylene blue, and various other structural analogues retain the ability to inhibit MAO‐A. Based on this, the present study evaluated 22 dyes, many of which are structurally related to methylene blue, as potential inhibitors of human MAO‐A and MAO‐B. The results highlighted three dye compounds as good potency competitive and reversible MAO inhibitors, and which exhibit higher MAO inhibition than methylene blue: acridine orange, oxazine 170 and Darrow red. Acridine orange was found to be a MAO‐A specific inhibitor (IC50 = 0.017 μM), whereas oxazine 170 is a MAO‐B specific inhibitor (IC50 = 0.0065 μM). Darrow red was found to be a non‐specific MAO inhibitor (MAO‐A, IC50 = 0.059 μM; MAO‐B, IC50 = 0.065 μM). These compounds may be advanced for further testing and preclinical development, or be used as possible lead compounds for the future design of MAO inhibitors.

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Section: Methodsmentioning

confidence: 99%

Monoamine oxidase inhibition by selected dye compounds

Beer

Petzer

2019

Chem Biol Drug Des

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“…The dialysis buffer was replaced at 3 h and 7 h after the start of dialysis. As positive controls, dialysis of MAO-A and MAO-B was carried out in the presence of the irreversible inhibitors, pargyline (IC 50 = 13 μM) and (R)-deprenyl (IC 50 = 0.079 μM), respectively [18,32]. As negative control, dialysis was carried out in the absence of inhibitor.…”

Section: Ic 50 Determinationsmentioning

confidence: 99%

“…The substituents considered were the benzyloxy and 2-phenoxyethoxy moieties. Both these substituents have been shown to enhance the MAO inhibition potencies of caffeine derivatives, while the benzyloxy side chain has also been shown to yield good MAO inhibition when substituted on C6 and C7 of 1-tetralone [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

The evaluation of 1-tetralone and 4-chromanone derivatives as inhibitors of monoamine oxidase

et al. 2020

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Monoamine oxidase (MAO) is of much clinical relevance, and inhibitors of this enzyme are used in the treatment for neuropsychiatric and neurodegenerative disorders such as depression and Parkinson's disease. The present study synthesises and evaluates the MAO inhibition properties of a series of 33 1-tetralone and 4-chromanone derivatives in an attempt to discover high-potency compounds and to expand on the structure-activity relationships of MAO inhibition by these classes. Among these series, eight submicromolar MAO-A inhibitors and 28 submicromolar MAO-B inhibitors are reported, with all compounds acting as specific inhibitors of the MAO-B isoform. The most potent inhibitor was a 1-tetralone derivative (1h) with IC 50 values of 0.036 and 0.0011 µM for MAO-A and MAO-B, respectively. Interestingly, with the reduction of 1-tetralones to the corresponding alcohols, a decrease in MAO inhibition potency is observed. Among these 1-tetralol derivatives, 1p (IC 50 = 0.785 μM) and 1o (IC 50 = 0.0075 μM) were identified as particularly potent inhibitors of MAO-A and MAO-B, respectively. Potent compounds such as those reported here may act as leads for the future development of MAO-B specific inhibitors.

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“…The dialysis buffer was replaced with fresh buffer at 3 h and 7 h after the start of dialysis. As positive controls, MAO-A and MAO-B were similarly pre-incubated and dialyzed in the presence of the irreversible inhibitor, pargyline (IC 50 = 13 µM) and selegiline (IC 50 = 0.079 µM), respectively [39,40]. As negative control, dialysis of the enzyme was carried out in the absence of the inhibitor.…”

Section: Dialysis Studiesmentioning

confidence: 99%

Monoamine Oxidase Inhibition by Kavalactones from Kava (Piper Methysticum)

et al. 2019

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Monoamine oxidases (MAOs) are key metabolic enzymes for neurotransmitter and dietary amines and are targets for the treatment of neuropsychiatric and neurodegenerative disorders. This study examined the MAO inhibition potential of kavain and other kavalactones from the roots of kava (Piper methysticum), a plant that has been used for its anxiolytic properties. (±)-Kavain was found to be a good potency in vitro inhibitor of human MAO-B with an IC50 of 5.34 µM. (±)-Kavain is a weaker MAO-A inhibitor with an IC50 of 19.0 µM. Under the same experimental conditions, the reference MAO inhibitor, curcumin, displays IC50 values of 5.01 µM and 2.55 µM for the inhibition of MAO-A and MAO-B, respectively. It was further established that (±)-kavain interacts reversibly and competitively with MAO-A and MAO-B with enzyme-inhibitor dissociation constants (Ki) of 7.72 and 5.10 µM, respectively. Curcumin in turn, displays a Ki value of 3.08 µM for the inhibition of MAO-A. Based on these findings, other kavalactones (dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin) were also evaluated as MAO inhibitors in this study. Yangonin proved to be the most potent MAO inhibitor with IC50 values of 1.29 and 0.085 µM for MAO-A and MAO-B, respectively. It may be concluded that some of the central effects (e.g., anxiolytic) of kava may be mediated by MAO inhibition.

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

Cited by 17 publications

References 18 publications

Monoamine oxidase inhibition by selected dye compounds

Monoamine oxidase inhibition by selected dye compounds

The evaluation of 1-tetralone and 4-chromanone derivatives as inhibitors of monoamine oxidase

Monoamine Oxidase Inhibition by Kavalactones from Kava (Piper Methysticum)

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