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2000
Volume 33, Issue 7
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Introduction

Prolyl-specific oligopeptidase (POP), one of the brain's highly expressed enzymes, is an important target for the therapy of central nervous system disorders, notably autism spectrum disorder, schizophrenia, Parkinson's, Alzheimer's disease, and dementia.

Methods

The current study was designed to investigate 2,4-bis(trifluoromethyl) benzaldehyde-based thiosemicarbazones as POP inhibitors to treat the above-mentioned disorders. A variety of techniques, such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and Fourier-transform infrared spectroscopy (FTIR), were used for the structural confirmation of synthesized compounds. After evaluation, all of these compounds were found to be prominent inhibitors of the POP enzyme (IC 10.14 - 41.73 M).

Results

Compound 3a emerged as the most active compound (IC 10.14 ± 0.72 M) of the series. The kinetic study of the most active 3a ( =13.66 0.0012 M) indicated competitive inhibition of the aforementioned enzyme.

Conclusion

Moreover, molecular docking depicted a noticeable role of thiosemicarbazide moiety in the binding of these molecules within the active site of the POP enzyme.

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Synthesis of 2,4-bis(trifluoromethyl)benzaldehyde Hybrid Thiosemicarbazones as Prolyl Oligopeptidase Inhibitors for Neurodegenerative Disorders and their In silico Analysis
Curr. Med. Chem. 33, 1436 (2026); https://doi.org/10.2174/0109298673325023240909101327
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  • Article Type:     Research Article
Keyword(s): 2,4-bis(trifluoromethyl)benzaldehyde; kinetics; magnetic resonance; molecular docking; prolyl endo-peptidase inhibitors; thiosemicarbazone

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