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-d...
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| Main Authors: | , , , , , , , |
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| Format: | Book |
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MDPI AG,
2022-04-01T00:00:00Z.
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| Online Access: | Connect to this object online. |
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| Summary: | 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<sub>2</sub>O<sub>2</sub>-induced oxidative stress on SH-SY5Y cells and in a model of 6-OHDA-induced neurotoxicity in rat brain synaptosomes, where the dihydroxy compounds <b>3h</b> and <b>3i</b> 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 <b>3h</b> 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-<b>3h</b> and <b>3j</b>, <b>3q</b>. The catecholic compound <b>3h</b> 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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| Item Description: | 10.3390/antiox11050884 2076-3921 |