Fragment screening revealed that tyramine binds to the active site of the Alzheimer's disease drug target BACE-1. Hit expansion by selection of compounds from the Roche compound library identified tyramine derivatives with improved binding affinities as monitored by surface plasmon resonance. X-ray structures show that the amine of the tyramine fragment hydrogen-bonds to the catalytic water molecule. Structure-guided ligand design led to the synthesis of further low molecular weight compounds that are starting points for chemical leads.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2008.01.032 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Investigation of bioactive components responsible for the antibacterial and anti-biofilm activities of by LC-QTOF-MS/MS analysis and molecular docking.
RSC Adv
April 2024
Pharmaceutical Microbiology Department, Faculty of Pharmacy, Tanta University Tanta 31527 Egypt.
Article Synopsis
- This study is the first to profile the metabolites of a wild desert plant from the Amaranthaceae family using LC-QTOF-MS/MS, identifying 66 known compounds including catecholamines, phenolic acids, and a novel tyramine derivative.
- The research addresses taxonomical challenges within the genus by providing insights into the plant's chemical fingerprint and its phylogenetic relationships with other species.
- The methanolic extract of the plant showed antibacterial properties, with a minimum inhibitory concentration ranging from 32 to 256 μg/mL, and significantly reduced biofilm formation and violacein production, attributed to specific compounds binding to a transcriptional activator.
Riparin II-type benzamides as novel antibiofilm agents against dermatophytes: chemical synthesis, in vitro, ex vivo and in silico evaluation.
J Antimicrob Chemother
March 2024
Fungi Research Group, Academic Unit of Health in the Education and Health Center, Federal University of Campina Grande, Cuité, Brazil.
Background: The ability of dermatophytes to develop biofilms in host tissues confers physical and biochemical resistance to antifungal drugs. Therefore, research to find new compounds against dermatophyte biofilm is crucial.
Objectives: To evaluate the antifungal activity of riparin II (RIP2), nor-riparin II (NOR2) and dinor-riparin II (DINOR2) against Trichophyton rubrum, Microsporum canis and Nannizzia gypsea strains.
Assessment of cypermethrin and amitraz resistance and molecular profiling of voltage-gated sodium channel and octopamine tyramine genes of .
Front Cell Infect Microbiol
June 2023
Department of Zoology, Abdul Wali Khan University Mardan, Mardan, Pakistan.
Control of ticks and tick-borne pathogens is a priority for human and animal health. Livestock-holders extensively rely on acaricide applications for tick control. Different groups of acaricides including cypermethrin and amitraz have been consistently used in Pakistan.
View Article and Find Full Text PDFMolecular Characterization of Octopamine/Tyramine Receptor Gene of Amitraz-Resistant () Ticks from Uganda.
Microorganisms
November 2022
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-Cho, Obihiro 080-8555, Japan.
We previously reported the emergence of amitraz-resistant () ticks in the western region of Uganda. This study characterized the octopamine/tyramine receptor gene (OCT/Tyr) of amitraz-resistant and -susceptible (.) ticks from four regions of Uganda.
View Article and Find Full Text PDFDiscovery of Trace Amine Associated Receptor 1 (TAAR1) Agonist 2-(5-(4'-Chloro-[1,1'-biphenyl]-4-yl)-4-1,2,4-triazol-3-yl)ethan-1-amine (LK00764) for the Treatment of Psychotic Disorders.
Biomolecules
November 2022
Institute of Translational Biomedicine, Saint Petersburg State University, 199034 Saint Petersburg, Russia.
A focused in-house library of about 1000 compounds comprising various heterocyclic motifs in combination with structural fragments similar to β-phenethylamine (PEA) or tyramine was screened for the agonistic activity towards trace amine-associated receptor 1 (TAAR1). The screening yielded two closely related hits displaying EC50 values in the upper submicromolar range. Extensive analog synthesis and testing for TAAR1 agonism in a BRET-based cellular assay identified compound (LK00764) with EC = 4.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!