Revisiting capsaicin and nonivamide: Their analogs exert strong inhibitory activity against cholinesterases

The scientific community has long been interested in capsaicin, and the extensive hunt for AChE and BChE enzyme inhibitors is still ongoing. In this investigation analogs of capsaicin, such as the pharmaceutical nonivamide, which is preferred in clinical settings for the topical treatment of pain, w...

Full description

Saved in:
Bibliographic Details
Main Authors: Niels V. Heise, Jeremy Quast, René Csuk
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:European Journal of Medicinal Chemistry Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2772417424000724
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850137997887930368
author Niels V. Heise
Jeremy Quast
René Csuk
author_facet Niels V. Heise
Jeremy Quast
René Csuk
author_sort Niels V. Heise
collection DOAJ
description The scientific community has long been interested in capsaicin, and the extensive hunt for AChE and BChE enzyme inhibitors is still ongoing. In this investigation analogs of capsaicin, such as the pharmaceutical nonivamide, which is preferred in clinical settings for the topical treatment of pain, were explored in the search for appropriate inhibitors. Thus, to test their inhibitory effect on AChE and BChE, we synthesized a short series of derivatives derived from vanillylamide. Consequently, it was discovered that compounds 12, 34, and 35, which have Ki values in the sub-micromolar concentration range, are especially effective inhibitors. Compound 12 demonstrated dual mixed-type (competitive/uncompetitive) inhibitory activity for both enzymes; compound 34 showed selective mixed-type inhibitory activity for AChE, and compound 35 was found to have selective uncompetitive activity for AChE.
format Article
id doaj-art-4bf4932214da4f569189226fe2ecbab2
institution OA Journals
issn 2772-4174
language English
publishDate 2024-12-01
publisher Elsevier
record_format Article
series European Journal of Medicinal Chemistry Reports
spelling doaj-art-4bf4932214da4f569189226fe2ecbab22025-08-20T02:30:42ZengElsevierEuropean Journal of Medicinal Chemistry Reports2772-41742024-12-011210020010.1016/j.ejmcr.2024.100200Revisiting capsaicin and nonivamide: Their analogs exert strong inhibitory activity against cholinesterasesNiels V. Heise0Jeremy Quast1René Csuk2Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120, Halle (Saale), GermanyMartin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120, Halle (Saale), GermanyCorresponding author.; Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120, Halle (Saale), GermanyThe scientific community has long been interested in capsaicin, and the extensive hunt for AChE and BChE enzyme inhibitors is still ongoing. In this investigation analogs of capsaicin, such as the pharmaceutical nonivamide, which is preferred in clinical settings for the topical treatment of pain, were explored in the search for appropriate inhibitors. Thus, to test their inhibitory effect on AChE and BChE, we synthesized a short series of derivatives derived from vanillylamide. Consequently, it was discovered that compounds 12, 34, and 35, which have Ki values in the sub-micromolar concentration range, are especially effective inhibitors. Compound 12 demonstrated dual mixed-type (competitive/uncompetitive) inhibitory activity for both enzymes; compound 34 showed selective mixed-type inhibitory activity for AChE, and compound 35 was found to have selective uncompetitive activity for AChE.http://www.sciencedirect.com/science/article/pii/S2772417424000724CapsaicinNonivamideCholinesteraseInhibitor
spellingShingle Niels V. Heise
Jeremy Quast
René Csuk
Revisiting capsaicin and nonivamide: Their analogs exert strong inhibitory activity against cholinesterases
European Journal of Medicinal Chemistry Reports
Capsaicin
Nonivamide
Cholinesterase
Inhibitor
title Revisiting capsaicin and nonivamide: Their analogs exert strong inhibitory activity against cholinesterases
title_full Revisiting capsaicin and nonivamide: Their analogs exert strong inhibitory activity against cholinesterases
title_fullStr Revisiting capsaicin and nonivamide: Their analogs exert strong inhibitory activity against cholinesterases
title_full_unstemmed Revisiting capsaicin and nonivamide: Their analogs exert strong inhibitory activity against cholinesterases
title_short Revisiting capsaicin and nonivamide: Their analogs exert strong inhibitory activity against cholinesterases
title_sort revisiting capsaicin and nonivamide their analogs exert strong inhibitory activity against cholinesterases
topic Capsaicin
Nonivamide
Cholinesterase
Inhibitor
url http://www.sciencedirect.com/science/article/pii/S2772417424000724
work_keys_str_mv AT nielsvheise revisitingcapsaicinandnonivamidetheiranalogsexertstronginhibitoryactivityagainstcholinesterases
AT jeremyquast revisitingcapsaicinandnonivamidetheiranalogsexertstronginhibitoryactivityagainstcholinesterases
AT renecsuk revisitingcapsaicinandnonivamidetheiranalogsexertstronginhibitoryactivityagainstcholinesterases