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Design, synthesis, and biological evaluation of new urolithin amides as multitarget agents against Alzheimer's disease
Author(s) -
Shukur Karar T.,
Ercetin Tugba,
Luise Chiara,
Sippl Wolfgang,
Sirkecioglu Okan,
Ulgen Mert,
Coskun Goknil P.,
Yarim Mine,
Gazi Mustafa,
Gulcan Hayrettin O.
Publication year - 2021
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.202000467
Subject(s) - acetylcholinesterase , chemistry , butyrylcholinesterase , monoamine oxidase , amide , monoamine oxidase b , docking (animal) , stereochemistry , combinatorial chemistry , aché , pharmacology , enzyme , biochemistry , medicine , nursing
Abstract 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.