Neuroprotective and MAOB inhibitory effects of a series of caffeine-8-thioglycolic acid amides

Kasabova-Angelova, Alexandra; Kondeva-Burdina, Magdalena; Mitkov, Javor; Georgieva, Maya; Tzankova, Virginia; Zlatkov, Alexander

doi:10.1590/s2175-97902019000318255

Cited by 9 publications

(4 citation statements)

References 30 publications

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“…Limited knowledge about the mechanisms of neurodegeneration in PD and the heterogeneity of the pathology are the main challenges in the field of neurology. New diagnostic methods, gene therapy 36 ,non-dopaminergic strategy for neuroprotection, xanthine derivatives research 37,38 , approaches for antagonism of adenosine A2A receptors, monoamine oxidase type-B inhibition (MAO-B) 39,40 , and deep-brain stimulation 41 are promising tools for achieving better clinical results in disease management.…”

Section: Discussionmentioning

confidence: 99%

Review of Medicine Utilization for Parkinson's Disease Management: The Bulgarian Perspective

Mitkova

Kamusheva

Kalpachka

et al. 2021

Journal of Public Health Research

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Background: Parkinson’s disease (PD), which occurs in 1% of the population, is the second most common neurodegenerative disorder. Despite the broad spectrum of PD manifestations and high disease prevalence, there are insufficient data on medicine utilization and prescription strategies. The purpose of the current study was to analyze published data concerning treatment approaches and to compare them with Bulgarian therapeutic practice.Design and methods: We conducted a systematic review of the PubMed and Google Scholar databases, and we calculated medicine utilization in Bulgaria during 2018 and 2019 using the WHO methodology.Results: The literature search identified a total of 311 publications, but only 12 met the inclusion criteria. Eleven studies pointed out that levodopa-containing medicine are the most frequently used, followed by dopamine agonists. The highest rate was found for levodopa-containing products and decarboxylase inhibitor (1.06 and 1.33 DDD/1000 inh/day), followed by anticholinergic Biperiden (0.494 and 0.455 DDD/1000 inh/day) during 2018 and 2019 in Bulgaria.Conclusion: Overall, the treatment approaches used in the last decade comply with guideline recommendations, despite variations in levodopa and dopamine agonist utilization. Even though new medicines have been approved for PD management, levodopa-containing products are still most often prescribed and used worldwide.

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Section: Discussionmentioning

confidence: 99%

Review of Medicine Utilization for Parkinson's Disease Management: The Bulgarian Perspective

Mitkova

Kamusheva

Kalpachka

et al. 2021

Journal of Public Health Research

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“…Inhibition of monoamine oxidase activity assay of recombinant human MAO-B (hMAO-B) was monitored by a fluorimetric assay that was slightly modified according to [ 47 ]. Amplex ® UltraRed reagent [ 48 ] was used for detection of the hydrogen peroxide and peroxidase activity in biological samples and enzymes.…”

Section: Methodsmentioning

confidence: 99%

New Indole-3-Propionic Acid and 5-Methoxy-Indole Carboxylic Acid Derived Hydrazone Hybrids as Multifunctional Neuroprotectors

et al. 2023

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In light of the known neuroprotective properties of indole compounds and the promising potential of hydrazone derivatives, two series of aldehyde-heterocyclic hybrids combining those pharmacophores were synthesized as new multifunctional neuroprotectors. The obtained derivatives of indole-3-propionic acid (IPA) and 5-methoxy-indole carboxylic acid (5MICA) had good safety profiles: Hemolytic effects < 5% (200 μM) and IC50 > 150 µM were found in the majority of the SH-SY5Y and bEnd3 cell lines. The 2,3-dihydroxy, 2-hydroxy-4-methoxy, and syringaldehyde derivatives of 5MICA exhibited the strongest neuroprotection against H2O2-induced oxidative stress in SH-SY5Y cells and 6-OHDA-induced neurotoxicity in rat-brain synaptosomes. All the compounds suppressed the iron-induced lipid peroxidation. The hydroxyl derivatives were also the most active in terms of deoxyribose-degradation inhibition, whereas the 3,4-dihydroxy derivatives were able to decrease the superoxide-anion generation. Both series of compounds showed an increased inhibition of hMAO-B, with greater expression detected in the 5MICA hybrids. The in vitro BBB model with the bEnd3 cell line showed that some compounds increased the permeability of the endothelial monolayer while maintaining the tight junctions. The combined results demonstrated that the derivatives of IPA and 5MICA showed strong neuroprotective, antioxidant, MAO-B inhibitory activity and could be considered as prospective multifunctional compounds for the treatment of neurodegenerative disorders.

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“…The monoamine oxidase type B activity was assayed on recombinant human MAOB using a fluorimetric method applying Amplex ® UltraRed reagent [ 51 ] with small modifications [ 52 ] where tyramine hydrochloride was used as substrate and Selegiline as a positive control.…”

Section: Methodsmentioning

confidence: 99%

In Silico Evaluation and In Vitro Determination of Neuroprotective and MAO-B Inhibitory Effects of Pyrrole-Based Hydrazones: A Therapeutic Approach to Parkinson’s Disease

et al. 2022

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Parkinson’s disease is a huge burden in modern medicinal practice. A serious drawback of current antiparkinsonian therapy is its symptomatic nature. This directed our investigations in the search for new more potent derivatives, affecting not only the loss of dopaminergic neurons but also the oxidative damage of neuronal cells. Thus in vitro neurotoxicity and neuroprotective analysis on a group of N-pyrrolyl hydrazide–hydrazones were performed. The neurotoxicity of the target derivatives was determined on a subcellular level in isolated rat synaptosomes, mitochondria and microsomes determining their effect on cellular vitality, GSH depletion and MDA production. The neuroprotective effects of the evaluated hydrazones were measured in three models of induced oxidative stress: 6-OHDA, t-BuOOH and Fe2+/AA-induced lipid peroxidation. Molecular docking simulations along with in vitro evaluation of MAO-B inhibitory potential of the target molecules were also performed. The results identified the ethyl 5-(4-bromophenyl)-1-(3-hydrazinyl-3-oxopropyl)-2-methyl-1H-pyrrole-3-carboxylate (12) as the most promising compound with the lowest neurotoxicity and highest neuroprotection on all evaluated parameters and inhibiting the hMAOB enzyme by 50%, comparable with the activity of the reference, Selegiline. The compatibility of the in silico and in vitro evaluations is a good prerequisite for these methods to be applied in future assessment of pyrrole-based compounds as anti-Parkinson agents.

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Neuroprotective and MAOB inhibitory effects of a series of caffeine-8-thioglycolic acid amides

Cited by 9 publications

References 30 publications

Review of Medicine Utilization for Parkinson's Disease Management: The Bulgarian Perspective

Review of Medicine Utilization for Parkinson's Disease Management: The Bulgarian Perspective

New Indole-3-Propionic Acid and 5-Methoxy-Indole Carboxylic Acid Derived Hydrazone Hybrids as Multifunctional Neuroprotectors

In Silico Evaluation and In Vitro Determination of Neuroprotective and MAO-B Inhibitory Effects of Pyrrole-Based Hydrazones: A Therapeutic Approach to Parkinson’s Disease

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