Azure B and a synthetic structural analogue of methylene blue, ethylthioninium chloride, present with antidepressant-like properties

Delport, Anzelle; Harvey, Brian H.; Petzer, Anél; Petzer, Jacobus P.

doi:10.1016/j.lfs.2014.10.005

Cited by 18 publications

(37 citation statements)

References 61 publications

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“…a Values are given as mean ± SD of triplicate determinations. MTT) cell viability assay was employed 48,49. Cytotoxicity was evaluated by exposing HeLa cells for 24 h to concentrations of 1 and 10 lM of the test compounds.…”

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confidence: 99%

Monoamine oxidase inhibitory activities of heterocyclic chalcones

Minders

Petzer

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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confidence: 99%

Monoamine oxidase inhibitory activities of heterocyclic chalcones

Minders

Petzer

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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“…Work in our own laboratory has demonstrated the structural characteristics of various methylene blue analogues, confirming that their antidepressant properties reside in the positively charged dimethylamino group. 310,311 This property enables these compounds to modulate the mitochondrial electron transport chain, affording them with potent antioxidant and neuroprotective properties.…”

Section: Compounds Targeting Nitric Oxidementioning

confidence: 99%

Neurodevelopmental Animal Models Reveal the Convergent Role of Neurotransmitter Systems, Inflammation, and Oxidative Stress as Biomarkers of Schizophrenia: Implications for Novel Drug Development

Möller

Swanepoel

Harvey

2015

ACS Chem. Neurosci.

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Schizophrenia is a life altering disease with a complex etiology and pathophysiology, and although antipsychotics are valuable in treating the disorder, certain symptoms and/or sufferers remain resistant to treatment. Our poor understanding of the underlying neuropathological mechanisms of schizophrenia hinders the discovery and development of improved pharmacological treatment, so that filling these gaps is of utmost importance for an improved outcome. A vast amount of clinical data has strongly implicated the role of inflammation and oxidative insults in the pathophysiology of schizophrenia. Preclinical studies using animal models are fundamental in our understanding of disease development and pathology as well as the discovery and development of novel treatment options. In particular, social isolation rearing (SIR) and pre- or postnatal inflammation (PPNI) have shown great promise in mimicking the biobehavioral manifestations of schizophrenia. Furthermore, the "dual-hit" hypothesis of schizophrenia states that a first adverse event such as genetic predisposition or a prenatal insult renders an individual susceptible to develop the disease, while a second insult (e.g., postnatal inflammation, environmental adversity, or drug abuse) may be necessary to precipitate the full-blown syndrome. Animal models that emphasize the "dual-hit" hypothesis therefore provide valuable insight into understanding disease progression. In this Review, we will discuss SIR, PPNI, as well as possible "dual-hit" animal models within the context of the redox-immune-inflammatory hypothesis of schizophrenia, correlating such changes with the recognized monoamine and behavioral alterations of schizophrenia. Finally, based on these models, we will review new therapeutic options, especially those targeting immune-inflammatory and redox pathways.

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“…The structures of methylene blue, azure A, azure B and ethylthioninium chloride (ETC) (Delport et al, ; Harvey et al, ; Petzer et al, )…”

Section: Introductionmentioning

confidence: 99%

“…Azure B is characterized as a potent reversible human MAO-A inhibitor (IC 50 = 0.01 µM) and a MAO-B inhibitor (IC 50 = 0.97 µM) (Petzer, Harvey, Wegener, & Petzer, 2012). A structural analogue of methylene blue namely ethylthioninium chloride (ETC) also exhibits MAO-A (IC 50 = 0.51 µM) and MAO-B (IC 50 = 0.59 µM) inhibition activities (Delport, Harvey, Petzer, & Petzer, 2014). The antidepressant properties of azure B and ETC were evaluated and confirmed by studies conducted with animal models (Delport et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…A structural analogue of methylene blue namely ethylthioninium chloride (ETC) also exhibits MAO-A (IC 50 = 0.51 µM) and MAO-B (IC 50 = 0.59 µM) inhibition activities (Delport, Harvey, Petzer, & Petzer, 2014). The antidepressant properties of azure B and ETC were evaluated and confirmed by studies conducted with animal models (Delport et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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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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Azure B and a synthetic structural analogue of methylene blue, ethylthioninium chloride, present with antidepressant-like properties

Cited by 18 publications

References 61 publications

Monoamine oxidase inhibitory activities of heterocyclic chalcones

Monoamine oxidase inhibitory activities of heterocyclic chalcones

Neurodevelopmental Animal Models Reveal the Convergent Role of Neurotransmitter Systems, Inflammation, and Oxidative Stress as Biomarkers of Schizophrenia: Implications for Novel Drug Development

Monoamine oxidase inhibition by selected dye compounds

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