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

Abstract

Introduction

Prolyl oligopeptidase (POP) is a pivotal druggable target implicated in diverse biological processes and linked to the development of various ailments, including neurodegenerative disorders. While conventional peptide-based inhibitors have been a centerpiece, their limitations, such as restricted bioavailability, necessitate exploration of non-peptidic inhibitors for their therapeutic potential.

Methods

This study focuses on designing, synthesizing, and assessing morpholine-based hydrazones targeting the catalytic serine residue of POP. The hydrazones , reported as moderately potent analogs compared to the renowned Z-Pro-Prolinal, demonstrated POP inhibition with IC values ranging from 13.60 ± 2.51 to 36.51 ± 1.82 μM. The derivative , with an IC of 13.60 ± 2.51 μM, emerged as the most potent inhibitor.

Results

Moreover, the kinetic study of compound indicated that it exhibited concentration-dependent type of inhibition. docking studies of revealed robust interactions in the POP enzyme's active site, yielding a docking score of ˗6.30 Kcal/mol, consistent with experimental results.

Conclusion

All findings underscored the potential of synthesized derivatives for drug development.

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2026-02-25

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Morpholine-tethered Novel Hydrazones as Promising Non-peptidic Prolyl Oligopeptidase (POP) Inhibitors: Synthesis <span class="jp-italic">In Vitro</span> and <span class="jp-italic">In Silico&nbsp;</span> Studies
Curr. Med. Chem. 33, 1419 (2026); https://doi.org/10.2174/0109298673304532240911070202
/content/journals/cmc/10.2174/0109298673304532240911070202
/content/journals/cmc/10.2174/0109298673304532240911070202
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  • Article Type:     Research Article
Keyword(s): antimicrobial; hydrazones; molecular docking; morpholine; prolyl endopeptidase (PEP); Prolyl oligopeptidase (POP)

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