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Study on the Neuroprotective, Radical-Scavenging and MAO-B Inhibiting Properties of New Benzimidazole Arylhydrazones as Potential Multi-Target Drugs for the Treatment of Parkinson’s Disease

Oxidative stress is a key contributing factor in the complex degenerating cascade in Parkinson’s disease. The inhibition of MAO-B affords higher dopamine bioavailability and stops ROS formation. The incorporation of hydroxy and methoxy groups in the arylhydrazone moiety of a new series of 1,3-disubs...

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Autores principales: Anastassova, Neda, Aluani, Denitsa, Hristova-Avakumova, Nadya, Tzankova, Virginia, Kondeva-Burdina, Magdalena, Rangelov, Miroslav, Todorova, Nadezhda, Yancheva, Denitsa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138090/
https://www.ncbi.nlm.nih.gov/pubmed/35624746
http://dx.doi.org/10.3390/antiox11050884
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author Anastassova, Neda
Aluani, Denitsa
Hristova-Avakumova, Nadya
Tzankova, Virginia
Kondeva-Burdina, Magdalena
Rangelov, Miroslav
Todorova, Nadezhda
Yancheva, Denitsa
author_facet Anastassova, Neda
Aluani, Denitsa
Hristova-Avakumova, Nadya
Tzankova, Virginia
Kondeva-Burdina, Magdalena
Rangelov, Miroslav
Todorova, Nadezhda
Yancheva, Denitsa
author_sort Anastassova, Neda
collection PubMed
description Oxidative stress is a key contributing factor in the complex degenerating cascade in Parkinson’s disease. The inhibition of MAO-B affords higher dopamine bioavailability and stops ROS formation. The incorporation of hydroxy and methoxy groups in the arylhydrazone moiety of a new series of 1,3-disubstituted benzimidazole-2-thiones could increase the neuroprotective activity. In vitro safety evaluation on SH-SY5Y cells and rat brain synaptosomes showed a strong safety profile. Antioxidant and neuroprotective effects were evaluated in H(2)O(2)-induced oxidative stress on SH-SY5Y cells and in a model of 6-OHDA-induced neurotoxicity in rat brain synaptosomes, where the dihydroxy compounds 3h and 3i demonstrated the most robust neuroprotective and antioxidant activity, more pronounced than the reference melatonin and rasagiline. Statistically significant MAO-B inhibitory effects were exerted by some of the compounds where again the catecholic compound 3h was the most potent inhibitor similar to selegiline and rasagiline. The most potent antioxidant effect in the ferrous iron induced lipid peroxidation assay was observed for the three catechols—3h and 3j, 3q. The catecholic compound 3h showed scavenging capability against superoxide radicals and antioxidant effect in the iron/deoxyribose system. The study outlines a perspective multifunctional compound with the best safety profile, neuroprotective, antioxidant and MAO-B inhibiting properties.
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spelling pubmed-91380902022-05-28 Study on the Neuroprotective, Radical-Scavenging and MAO-B Inhibiting Properties of New Benzimidazole Arylhydrazones as Potential Multi-Target Drugs for the Treatment of Parkinson’s Disease Anastassova, Neda Aluani, Denitsa Hristova-Avakumova, Nadya Tzankova, Virginia Kondeva-Burdina, Magdalena Rangelov, Miroslav Todorova, Nadezhda Yancheva, Denitsa Antioxidants (Basel) Article Oxidative stress is a key contributing factor in the complex degenerating cascade in Parkinson’s disease. The inhibition of MAO-B affords higher dopamine bioavailability and stops ROS formation. The incorporation of hydroxy and methoxy groups in the arylhydrazone moiety of a new series of 1,3-disubstituted benzimidazole-2-thiones could increase the neuroprotective activity. In vitro safety evaluation on SH-SY5Y cells and rat brain synaptosomes showed a strong safety profile. Antioxidant and neuroprotective effects were evaluated in H(2)O(2)-induced oxidative stress on SH-SY5Y cells and in a model of 6-OHDA-induced neurotoxicity in rat brain synaptosomes, where the dihydroxy compounds 3h and 3i demonstrated the most robust neuroprotective and antioxidant activity, more pronounced than the reference melatonin and rasagiline. Statistically significant MAO-B inhibitory effects were exerted by some of the compounds where again the catecholic compound 3h was the most potent inhibitor similar to selegiline and rasagiline. The most potent antioxidant effect in the ferrous iron induced lipid peroxidation assay was observed for the three catechols—3h and 3j, 3q. The catecholic compound 3h showed scavenging capability against superoxide radicals and antioxidant effect in the iron/deoxyribose system. The study outlines a perspective multifunctional compound with the best safety profile, neuroprotective, antioxidant and MAO-B inhibiting properties. MDPI 2022-04-29 /pmc/articles/PMC9138090/ /pubmed/35624746 http://dx.doi.org/10.3390/antiox11050884 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Anastassova, Neda
Aluani, Denitsa
Hristova-Avakumova, Nadya
Tzankova, Virginia
Kondeva-Burdina, Magdalena
Rangelov, Miroslav
Todorova, Nadezhda
Yancheva, Denitsa
Study on the Neuroprotective, Radical-Scavenging and MAO-B Inhibiting Properties of New Benzimidazole Arylhydrazones as Potential Multi-Target Drugs for the Treatment of Parkinson’s Disease
title Study on the Neuroprotective, Radical-Scavenging and MAO-B Inhibiting Properties of New Benzimidazole Arylhydrazones as Potential Multi-Target Drugs for the Treatment of Parkinson’s Disease
title_full Study on the Neuroprotective, Radical-Scavenging and MAO-B Inhibiting Properties of New Benzimidazole Arylhydrazones as Potential Multi-Target Drugs for the Treatment of Parkinson’s Disease
title_fullStr Study on the Neuroprotective, Radical-Scavenging and MAO-B Inhibiting Properties of New Benzimidazole Arylhydrazones as Potential Multi-Target Drugs for the Treatment of Parkinson’s Disease
title_full_unstemmed Study on the Neuroprotective, Radical-Scavenging and MAO-B Inhibiting Properties of New Benzimidazole Arylhydrazones as Potential Multi-Target Drugs for the Treatment of Parkinson’s Disease
title_short Study on the Neuroprotective, Radical-Scavenging and MAO-B Inhibiting Properties of New Benzimidazole Arylhydrazones as Potential Multi-Target Drugs for the Treatment of Parkinson’s Disease
title_sort study on the neuroprotective, radical-scavenging and mao-b inhibiting properties of new benzimidazole arylhydrazones as potential multi-target drugs for the treatment of parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138090/
https://www.ncbi.nlm.nih.gov/pubmed/35624746
http://dx.doi.org/10.3390/antiox11050884
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