Inhibition of rat liver mitochondrial monoamine oxidase by hydrazine-thiazole derivatives: structure-activity relationships

Raciti, G.; Mazzone, Patrizia; Raudino, Antonio; Mazzone, G; Cambria, Antonio

doi:10.1016/0968-0896(95)00137-6

Cited by 32 publications

(16 citation statements)

References 22 publications

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“…These data are also consistent with the Michelis-Menten plot analysis that revealed that AOZ acts in a non-competitive manner in contrast to HEH which seems to affect directly the active site of the enzyme causing irreversible inhibition and the previously mentioned characteristic optical absorption at 400 nm. The non-competitive inhibitory effect observed for AOZ agrees with previous studies performed to investigate the relationship between chemical structure and inhibitory activity of some hydrazine-thiazole derivatives on rat liver mitochondria MAO (Tipton 1994, Raciti et al 1995. Raciti et al demonstrated that numerous compounds belonging to structurally diverse substituted hydrazines behave as non-competitive MAO inhibitors.…”

Section: Discussionsupporting

confidence: 89%

Identification of a furazolidone metabolite responsible for the inhibition of amino oxidases

2003

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1 Furazolidone, a drug widely used in human and veterinary medicine, exhibits inhibition of monoamine oxidase activity, as observed in the tissues of a number of different animal species, including man. The aim of the current study was to determine which of the two possible metabolites, 3-amino-2-oxazolidone (AOZ) or beta-hydroxyethylhydrazine (HEH), a well-known carcinogenic compound, is involved in the toxicological effects reported. 2 A new spectrometric method was set up to differentiate intracellular HEH from AOZ inside cells. This method works well at low pH where both AOZ and HEH are free in solution and available to react with the chemical chromophore (DAB). 3 The results confirm that furazolidone has to be metabolized in the intact cell in order to exhibit mitochondrial monoamine oxidase inhibition, whereas AOZ itself is able to exert a reversible monoamine oxidase inhibition. AOZ also inhibits bovine serum amino oxidase. On the contrary, HEH gives irreversible inhibition of both enzymes. However, the reversible nature of the AOZ inhibition with respect to HEH suggests that the two metabolites act by different mechanisms which do not require the biotransformation of AOZ to HEH. 4 Cell lysates, previously incubated with AOZ, were directly analysed and the formation of HEH from AOZ was not detected, supporting the conclusion that the amino oxidase inhibition observed on treatment with furazolidone was attributable to AOZ and not to HEH.

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Section: Discussionsupporting

confidence: 89%

Identification of a furazolidone metabolite responsible for the inhibition of amino oxidases

2003

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“…In Table 3, brain MAO activity has a positive correlation with brain and liver lipid peroxidation, but there is no correlation between liver MAO activity and brain or liver lipid peroxidation. This may be due to the reason of different functions between brain MAO (for amine neurotransmitters transformation) and liver MAO (for foreign amine compounds detoxification) ( 42 ) .…”

Section: Discussionmentioning

confidence: 99%

Both inorganic and organic selenium supplements can decrease brain monoamine oxidase B enzyme activity in adult rats

2008

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It has been observed that the levels of brain monoamine oxidase B (MAO-B) increase during ageing. MAO catalyses the oxidative deamination of neurotransmitters, in which the by-product H2O2 is subsequently generated. Se exists naturally in inorganic and organic forms and is considered to play a key role in antioxidation functioning. The objective of the present study was to investigate two chemical forms of Se compounds for their inhibition effect on rat brain MAO-B. The total antioxidant capacity and lipid peroxidation of rats were also examined. The rats (age 7 weeks) were divided into four groups: the control group, tocopherol group (T group, positive control), selenite group (SE group, representing the inorganic Se group) and seleno-yeast group (SY group, representing the organic Se group). The rats were fed for 11 weeks with normal diets and 12 weeks with test diets. The serum total antioxidant capacity of the SE and SY groups was significantly higher than that in the control and T groups. In rat brains and livers, the lipid peroxidation levels were significantly decreased in the T, SE and SY groups. MAO-B activity showed a significant decrease in the T, SE and SY groups in rat brains but no significant change could be noted in the rat livers. In conclusion, the present study indicates that inorganic or organic Se supplementation can decrease the brain MAO-B enzyme activity in adult rats and can be accomplished by the effect of the Se antioxidation capability.

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“…Previously it was reported that the thiazole motif could produce irreversible inhibition of MAO (Raciti et al, 1995). Therefore although the hydrazide motif causes hepatotoxicity when targeting MAO’s, the thiazole motif may be protective against Alzheimer’s disease through its inhibition of MAOs.…”

Section: Small Molecule Inhibitors Of Protein Aggregationmentioning

confidence: 99%

Tau as a therapeutic target in neurodegenerative disease

Himmelstein

Ward

Lancia

et al. 2012

Pharmacology & Therapeutics

100

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Tau is a microtubule-associated protein thought to help modulate the stability of neuronal microtubules. In tauopathies, including Alzheimer’s disease and several frontotemporal dementias, tau is abnormally modified and misfolded resulting in its disassociation from microtubules and the generation of pathological lesions characteristic for each disease. A recent surge in the population of people with neurodegenerative tauopathies has highlighted the immense need for disease-modifying therapies for these conditions, and new attention has focused on tau as a potential target for intervention. In the current work we summarize evidence linking tau to disease pathogenesis and review recent therapeutic approaches aimed at ameliorating tau dysfunction. The primary therapeutic tactics considered include kinase inhibitors and phosphatase activators, immunotherapies, small molecule inhibitors of protein aggregation, and microtubule-stabilizing agents. Although the evidence for tau-based treatments is encouraging, additional work is undoubtedly needed to optimize each treatment strategy for the successful development of safe and effective therapeutics.

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Inhibition of rat liver mitochondrial monoamine oxidase by hydrazine-thiazole derivatives: structure-activity relationships

Cited by 32 publications

References 22 publications

Identification of a furazolidone metabolite responsible for the inhibition of amino oxidases

Identification of a furazolidone metabolite responsible for the inhibition of amino oxidases

Both inorganic and organic selenium supplements can decrease brain monoamine oxidase B enzyme activity in adult rats

Tau as a therapeutic target in neurodegenerative disease

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