A5052773700- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Asymmetric Synthesis and Catalysis
- Chemical Reaction Mechanisms
- Coordination Chemistry and Organometallics
- Malaria Research and Control
- Neuroscience and Neuropharmacology Research
- Chemical Synthesis and Analysis
- Synthesis and pharmacology of benzodiazepine derivatives
- Insect Pest Control Strategies
- Chemical synthesis and alkaloids
- Synthetic Organic Chemistry Methods
- Insect and Pesticide Research
- Axial and Atropisomeric Chirality Synthesis
- Insect Resistance and Genetics
- Crystallography and molecular interactions
- Alzheimer's disease research and treatments
- Chemical Synthesis and Reactions
- Inorganic and Organometallic Chemistry
- Click Chemistry and Applications
- Nicotinic Acetylcholine Receptors Study
- Pesticide Exposure and Toxicity
- Synthesis and biological activity
Virginia Tech
2016-2025
University of Illinois Chicago
2023-2025
University of Illinois Urbana-Champaign
2023
Centre Hospitalier Universitaire de Bordeaux
2023
Hong Kong University of Science and Technology
1994-2021
University of Hong Kong
1996-2021
Institut de Myologie
2010-2020
Haute École Albert Jacquard
2016
University of Florida
2014
Molsoft (United States)
2014
Form-fitting chemistry in a protein mold is enabled by the use of 1,3-dipolar cycloaddition azides and alkynes. The enzyme acetylcholinesterase preferentially assembles one pair these reactants, each which bears group that binds to adjacent positions on structure (see picture), into 1,2,3-triazole adduct most potent noncovalent inhibitor yet developed. Supporting information for this article available WWW under http://www.wiley-vch.de/contents/jc_2002/2002/z18552_s.pdf or from author. Please...
The X-ray crystal structures were solved for complexes with Torpedo californica acetylcholinesterase of two bivalent tacrine derivative compounds in which the rings separated by 5- and 7-carbon spacers. spacer spans length active-site gorge, making sandwich interactions aromatic residues both catalytic anionic site (Trp84 Phe330) at bottom gorge peripheral near its mouth (Tyr70 Trp279). 5-carbon interacts a similar manner but shorter tether precludes interaction site. Although upper group...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRegioselective azide opening of 2,3-epoxy alcohols by [Ti(O-i-Pr)2(N3)2]: synthesis .alpha.-amino acidsMaurice Caron, Paul R. Carlier, and K. Barry SharplessCite this: J. Org. Chem. 1988, 53, 21, 5185–5187Publication Date (Print):October 1, 1988Publication History Published online1 May 2002Published inissue 1 October 1988https://pubs.acs.org/doi/10.1021/jo00256a063https://doi.org/10.1021/jo00256a063research-articleACS PublicationsRequest reuse...
Malaria remains a significant infectious disease that causes millions of clinical cases and >800,000 deaths per year. The Box is collection 400 commercially available chemical entities have antimalarial activity. contains 200 drug-like compounds, based on their oral absorption the presence known toxicophores, probe-like which are intended to represent broad structural diversity. These compounds confirmed activities against asexual intraerythrocytic stages Plasmodium falciparum low...
Maßgeschneiderte Chemie in einer Protein-Vorlage: Bei Reihe von Aziden und Alkinen, Reaktanten für eine 1,3-dipolare Cycloaddition, wird vom Enzym Acetylcholinesterase bevorzugt ein Paar Reaktionspartnern umgesetzt, denen beide an benachbarten Stellen der Proteinstruktur binden (siehe Bild). Das dabei gebildete 1,2,3-Triazol ist stärkste bisher entwickelte nichtkovalent gebundene Inhibitor dieses Enzym.
ABSTRACT Coxiella burnetii is a highly infectious bacterium and potential agent of bioterrorism. However, it has not been studied as extensively other biological agents, very few its proteins have structurally characterized. To address this situation, we undertook study critical metabolic enzymes in C. that great drug targets. We used high‐throughput techniques to produce novel crystal structures 48 these proteins. selected one protein, dihydrofolate reductase (CbDHFR), for additional work...
Dimeric acetylcholinesterase (AChE) inhibitors containing a single 9-amino-1,2,3,4-tetrahydroacridine (tacrine) unit were constructed in an effort to further delineate structural requirements for optimal binding the AChE peripheral site. Basic amines of differing hydrophobicity selected as site ligands, and each case, improvements inhibitory potency selectivity seen relative tacrine itself. IC50 values optimum dimers decrease significantly ligand was permuted series ammonia > dimethylamine...
The neuroprotective properties of bis(7)-tacrine, a novel dimeric acetylcholinesterase (AChE) inhibitor, on glutamate-induced excitotoxicity were investigated in primary cultured cerebellar granule neurons (CGNs). Exposure CGNs to 75 μm glutamate resulted neuronal apoptosis as demonstrated by Hoechst staining, TUNEL, and DNA fragmentation assays. bis(7)-tacrine treatment (0.01–1 μm) markedly reduced dose- time-dependent manners. However, donepezil other AChE inhibitors, even at...
Acetylcholinesterase (AChE) inhibitors improve the cognitive abilities of Alzheimer patients. (−)-Huperzine A [(−)-HupA], an alkaloid isolated from club moss, Huperzia serrata, is one such inhibitor, but search for more potent and selective drugs continues. Recently, alkylene-linked dimers 5-amino-5,6,7,8-tetrahydroquinolinone (hupyridone, 1a), a fragment HupA, were shown to serve as AChE than (−)-HupA monomeric 1a. We soaked two dimers, (S,S)-(−)-bis(10)-hupyridone [(S,S)-(−)-2a]...
Malaria continues to be one of the deadliest diseases worldwide, and emergence drug resistance parasites is a constant threat. Plasmodium utilize methylerythritol phosphate (MEP) pathway synthesize isopentenyl pyrophosphate (IPP) dimethylallyl (DMAPP), which are essential for parasite growth. Previously, we others identified that Box compound MMV008138 targets apicoplast growth inhibition by this can reversed supplementation IPP. Further work has revealed enzyme 2-C-methyl-d-erythritol...
Half the world's population is at risk of developing a malaria infection, which caused by parasites genus Plasmodium. Currently, resistance has been identified to all clinically available antimalarials, highlighting an urgent need develop novel compounds and better understand common mechanisms resistance. We previously tetrahydro-β-carboline compound, PRC1590, potently kills parasite. To its mechanism action, we selected for characterized PRC1590 in Plasmodium falciparum. Through vitro...
Abstract Background The Old World sand fly, Phlebotomus papatasi (Scopoli), a vector of zoonotic cutaneous leishmaniasis, is usually controlled by insecticides, including anticholinesterases. Previous studies have revealed 85% amino acid sequence identity recombinant P. acetylcholinesterase (r Pp AChE1) to mosquito AChE. They identified synthetic carbamates that selectively inhibited r AChE1 and circumvented the G119S mutation responsible for high-level resistance This study reports...
Simultaneous binding to the catalytic and peripheral sites of acetylcholinesterase (AChE) is invoked explain why new drug (S,S)-(−)-3, in which two aminoquinolinone units are linked by a dodecamethylene tether, more than twice as potent natural product huperzine A (−)-1 inhibition AChE. In contrast (±)-2, retains much functionality (−)-1, inhibits AChE only very weakly. Supporting information for this article available on WWW under http://www.wiley-vch.de/contents/jc_2002/2000/z14260_s.pdf...
Due to the putative involvement of dopaminergic circuits in depression, triple reuptake inhibitors are being developed as a new class antidepressant, which is hypothesized produce more rapid onset and better efficacy than current antidepressants selective for serotonin or norepinephrine neurotransmission. (<i>1S,2S</i>)-3-(Methylamino)-2-(naphthalen-2-yl)-1-phenylpropan-1-ol (PRC200-SS), inhibitor, potently bound human serotonin, norepinephrine, dopamine transporters with...