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  3. Exploring the Potential of Indole-3-acetic Acid Arylhydrazone Hybrids for Parkinson's Disease Treatment: A Comprehensive Evaluation of Neuroprotective, MAOB Inhibitory, and Antioxidant Properties

Exploring the Potential of Indole-3-acetic Acid Arylhydrazone Hybrids for Parkinson's Disease Treatment: A Comprehensive Evaluation of Neuroprotective, MAOB Inhibitory, and Antioxidant Properties

  • ACS Chem Neurosci. 2025 Mar 19;16(6):1161-1181. doi: 10.1021/acschemneuro.4c00838.
Neda Anastassova 1 2,  Magdalena Kondeva-Burdina 3,  Nadya Hristova-Avakumova 4,  Denitsa Stefanova 3,  Miroslav Rangelov 1,  Nadezhda Todorova 5,  Denitsa Yancheva 1 2
Affiliations

Affiliations

  • 1 Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Building 9, 1113 Sofia, Bulgaria.
  • 2 Department of Organic Chemistry, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, Bulgaria.
  • 3 Laboratory of Drug Metabolism and Drug Toxicity, Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.
  • 4 Department of Medical Physics and Biophysics, Faculty of Medicine, Medical University of Sofia, 2 Zdrave Str., 1431 Sofia, Bulgaria.
  • 5 Institute of Biodiversity and Ecosystem Research, Bulgarian Academy of Sciences, 2 Gagarin Str., 1113 Sofia, Bulgaria.
PMID: 40066901 DOI: 10.1021/acschemneuro.4c00838
Abstract

In the current study, a small series of five indole-3-acetic acid-derived arylhydrazone hybrids were synthesized and subjected to comprehensive evaluation of their neuropharmacological and radical-scavenging properties. Minimal neurotoxic effects were observed across diverse subcellular fractions, with particular emphasis on the compound 3a bearing a 2,3-dihydroxy moiety, exhibiting superior neuroprotective effects against H2O2-induced oxidative stress by preserving the cell viability up to 68%. Noteworthy neuroprotection was observed in 6-OHDA-induced neurotoxicity using isolated rat brain synaptosomes, with compounds 3b and 3c displaying prominent effects. Compound 3a demonstrated robust neuroprotective and antioxidant effects in models of tert-butyl hydroperoxide-induced oxidative stress on isolated rat brain mitochondria and nonenzyme-induced lipid peroxidation using isolated rat brain microsomes (Fe/AA). All compounds exhibited MAOB inhibition within the range of 0.130-0.493 μM, with compounds 3d, 3e, and 3a showing notable selectivity against hMAOB. Molecular docking studies further validated ligand binding within MAOB active sites. The derivatives demonstrated scavenging activity and antioxidant effects against various ROS types, with compound 3a consistently exhibiting the most potent activity. Structural modifications exerted discernible effects on scavenging capabilities and antioxidant effects, underscoring their potential therapeutic implications in neuroprotection and oxidative stress mitigation.

Keywords

MAOB inhibition; Parkinson’s disease; antioxidant activity; catechol; indole-3-acetic acid arylhydrazones; neuroprotection.

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