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

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-tostrong 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.

A mechanistic insight into the biological activities of urolithins as gut microbial metabolites of ellagitannins

“…A number of urolithin amide derivatives were recently synthesized and exhibited inhibitory effects against acetylcholinesterase, butyrylcholinesterase, and monoamine oxidase B. Some of them showed mild to potent inhibitory effects on amyloid aggregation (Shukur et al, 2021).…”

Urolithins: A Prospective Alternative against Brain Aging

“…Recently, pharmaceutical studies have been conducted on Uros. Several natural and synthetic Uro analogs exhibit inhibitory effects on various enzymes, including cholinesterases, MAO-B, and cyclooxygenases [ 145 , 146 ]. Therefore, Uros may be multi-target agents against neurodegenerative and neurological diseases.…”

BF3·OEt2 Catalyzed Cascade [4 + 2] Benzannulation of Vinyloxiranes with Coumarins to Construct Benzocoumarin Derivatives

“…The benzocoumarin scaffold plays a pivotal role in numerous bioactive natural compounds . For instance, Sarolactone displays exceptional antibacterial activity .…”