Huprine Y – Tryptophan heterodimers with potential implication to Alzheimer's disease treatment. (1st July 2021)

• Record Type: Journal Article
• Authors: Mezeiova, Eva; Hrabinova, Martina; Hepnarova, Vendula; Jun, Daniel; Janockova, Jana; Muckova, Lubica; Prchal, Lukas; Kristofikova, Zdena; Kucera, Tomas; Gorecki, Lukas; Chalupova, Katarina; Kunes, Jiri; Hroudova, Jana; Soukup, Ondrej; Korabecny, Jan
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 43(2021)
• Publication Date: 2021-07-01
• Subjects: Alzheimer's disease -- huprine Y -- l-Tryptophan -- Acetylcholinesterase -- Amyloid-beta -- Multi-target directed ligands; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.128100
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Huprine-tryptophan hybrids showed nanomolar inhibitory potency of cholinesterases. Huprine-tryptophan hybrids inhibited the formation of Aβ1-42 aggregates. The most potent inhibitor showed comparable anti-Aβ activity with reference myricetin. HupY-Trp heterodimers were effective inhibitors of nNOS comparable to bis(7)-THA. Abstract: The search for novel and effective therapeutics for Alzheimer's disease (AD) is the main quest that remains to be resolved. The goal is to find a disease-modifying agent able to confront the multifactorial nature of the disease positively. Herewith, a family of huprineY-tryptophan heterodimers was prepared, resulting in inhibition of cholinesterase and neuronal nitric oxide synthase enzymes, with effect against amyloid-beta (Aβ) and potential ability to cross the blood–brain barrier. Their cholinesterase pattern of behavior was inspected using kinetic analysis in tandem with docking studies. These heterodimers exhibited a promising pharmacological profile with strong implication in AD.