Design, synthesis, and biological evaluation of new urolithin amides as multitarget agents against Alzheimer's disease

A series of urolithin amide (i.e., URO‐4–URO‐10 and THU‐4–THU‐10) derivatives was designed and synthesized, and their chemical structures were confirmed with spectroscopic techniques and elemental analysis. The title compounds and synthesis intermediates (THU‐1–THU‐10 and URO‐1–URO‐10) were evaluate...

Full description

Saved in:

Bibliographic Details
Published in:	Archiv der Pharmazie (Weinheim) Vol. 354; no. 5; pp. e2000467 - n/a
Main Authors:	Shukur, Karar T., Ercetin, Tugba, Luise, Chiara, Sippl, Wolfgang, Sirkecioglu, Okan, Ulgen, Mert, Coskun, Goknil P., Yarim, Mine, Gazi, Mustafa, Gulcan, Hayrettin O.
Format:	Journal Article
Language:	English
Published:	Germany Wiley Subscription Services, Inc 01-05-2021
Subjects:	Alzheimer's disease amyloid beta antioxidant cholinesterase MAO‐B urolithins antioxidant MAO-B cholinesterase Alzheimer's disease urolithins amyloid beta
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	A series of urolithin amide (i.e., URO‐4–URO‐10 and THU‐4–THU‐10) derivatives was designed and synthesized, and their chemical structures were confirmed with spectroscopic techniques and elemental analysis. The title compounds and synthesis intermediates (THU‐1–THU‐10 and URO‐1–URO‐10) were evaluated for their potential to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase B (MAO‐B). Compounds THU‐4 and THU‐8 were found to be the most potent inhibitors for the cholinesterases and MAO‐B, respectively. The docking studies were also employed to evaluate the binding modes of the most active compounds with AChE, BuChE, and MAO‐B. Furthermore, the moderate‐to‐strong activities of the compounds were also displayed in amyloid‐beta inhibition and antioxidant assay systems. The results pointed out that the urolithin scaffold can be employed in drug design studies for the development of multitarget ligands acting on various cascades shown to be important within the pathophysiology of Alzheimer's disease. Urolithin amide (URO‐4–10 and THU‐4–10) derivatives were designed, synthesized, and evaluated for their potential to inhibit acetylcholinesterase, butyrylcholinesterase, and monoamine oxidase B (MAO‐B). Compounds THU‐4 and THU‐8 were found to be the most potent inhibitors for the cholinesterases and MAO‐B, respectively. Moderate/strong activities were found for amyloid‐beta inhibition, indicating that the urolithin scaffold can be employed in drug design for Alzheimer's disease.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0365-6233 1521-4184
DOI:	10.1002/ardp.202000467