A5070605420- Insect and Pesticide Research
- Nicotinic Acetylcholine Receptors Study
- Chemical synthesis and alkaloids
- DNA and Nucleic Acid Chemistry
- DNA Repair Mechanisms
- Metalloenzymes and iron-sulfur proteins
- Amphibian and Reptile Biology
- Chemical Reactions and Isotopes
- Receptor Mechanisms and Signaling
- Venomous Animal Envenomation and Studies
- Cancer therapeutics and mechanisms
- Insect Resistance and Genetics
- Ultrasound and Cavitation Phenomena
- Ion channel regulation and function
- Toxin Mechanisms and Immunotoxins
- Synthesis and Biological Evaluation
- Animal Ecology and Behavior Studies
- Crystallization and Solubility Studies
- Mass Spectrometry Techniques and Applications
- Various Chemistry Research Topics
- Chemical Reaction Mechanisms
- Insect symbiosis and bacterial influences
- Alkaloids: synthesis and pharmacology
- Plant-based Medicinal Research
- Advanced Synthetic Organic Chemistry
Indiana State University
2009-2024
St. John's University
2024
Indiana University – Purdue University Indianapolis
2011
National Institutes of Health
2003-2010
National Institute of Diabetes and Digestive and Kidney Diseases
2003-2009
Wabash College
2009
Radboud University Nijmegen
2008
GlaxoSmithKline (United Kingdom)
2006
Pennsylvania State University
2006
Georgetown University
2003
Seven cell lines expressing native and transfected nicotinic receptor subtypes were evaluated functionally by using fluorescent assays based on membrane potential calcium dynamics with “no-wash” dye systems. Both provided the same rank orders of potency for (±)-epibatidine, 2 S -(−)-nicotine, 7 R ,9 -(−)-cytisine, 1,1-dimethyl-4-phenylpiperazinium in a line rat α3β4 receptors. Nicotinic antagonists mecamylamine dihydro-β-erythroidine inhibited responses both assays. agonist antagonist...
Replication protein A (RPA) is a single-strand DNA-binding with essential roles in DNA replication, recombination, and repair. It necessary for the formation of preincision complex that required proper incision damaged nucleotides during We have previously identified small molecule inhibitors (SMI) ability to disrupt RPA-binding activity ssDNA. Further characterization these RPA was done using both lung ovarian cancer cell lines. Lung lines showed increased apoptotic death following...
Analytical HPLC fractionation, combined with an off-line 96-well fluorescent bioassay screen, has been developed and used for the separation screening of a natural product extract. This method was to guide isolation novel quinolizidine alkaloid from methanolic skin extracts Ecuadoran frog, Epipedobates tricolor. The structure determined on basis MS, IR, NMR analysis as (1R,10R)-1-acetamidoquinolizidine (alkaloid 196). We have named this compound epiquinamide, reflecting its origin structure....
The skin of the Ecuadorian poison frog Epipedobates anthonyi contains potent nicotinic agonists epibatidine (1) and N-methylepibatidine (3). In addition, a condensed tetracyclic congener has been identified with activity at acetylcholine receptors, but different selectivity than epibatidine. This rigid tetracycle named phantasmidine (4). Phantasmidine molecular formula C11H11N2OCl, shares chloropyridine moiety 1, also furan, pyrrolidine, cyclobutane rings. A combination GC-MS GC-FTIR...
There remains a high unmet medical need for safe oral therapy thrombotic disorders. The serine protease factor Xa (fXa), with its central role in the coagulation cascade, is among more promising targets anticoagulant and has been subject of intensive drug discovery efforts. Investigation hit from high-throughput screening identified series thiophene-substituted anthranilamides as potent nonamidine fXa inhibitors. Lead optimization by incorporation hydrophilic groups led to compounds...
A stereoselective synthesis of (+)-epiquinamide is presented in combination with determination the absolute configuration natural product. Key steps sequence involved chemoenzymatic formation an enantiomerically pure cyanohydrin, reductive cyclization to corresponding cyclic N,N-acetal, and subsequent conversion into a suitable N-acyliminium ion precursor enable construction second ring.
In 2003, we reported the isolation, structure elucidation, and pharmacology of epiquinamide (1), a novel alkaloid isolated from an Ecuadoran poison frog, Epipedobates tricolor. Since then, several groups, including ours, have undertaken synthetic efforts to produce this compound, which appeared initially be novel, β2-selective nicotinic acetylcholine receptor agonist. Based on prior chiral GC analysis natural samples, absolute was established as (1S,9aS)-1-acetamidoquinolizidine. We...
Understanding the origins of novel, complex phenotypes is a major goal in evolutionary biology. Poison frogs family Dendrobatidae have evolved novel ability to acquire alkaloids from their diet for chemical defense at least three times. However, taxon sampling has been biased towards colorful species, without similar attention paid inconspicuous ones that are often assumed be undefended. As result, our understanding how this group incomplete. Here, we provide new data showing that, contrast...
Animals that ingest toxins can become unpalatable and even toxic to predators parasites through toxin sequestration. Because most animals rapidly eliminate survive their ingestion, it is unclear how populations transition from susceptibility elimination tolerance accumulation as chemical defence emerges. Studies of have generally focused on species with active sequestration target-site insensitivity mutations or toxin-binding proteins permit survival without necessitating elimination. Here,...
Both antipodes of the Kishi lactam (3), versatile intermediate for synthesis perhydrohistrionicotoxin (pHTX) alkaloids, have been prepared. The synthetic route involved a "double Henry" condensation between glutaraldehyde and nitroacetal 5 giving meso dioxanyldiol 4 which was acetylated reduced to afford dioxane amide 8. Ultrasound-promoted deacetalization 8 followed by Wittig olefination reduction provided ester 10. Hydrolysis 10 with aqueous acid dehydrative cyclization...
Replication protein A (RPA) is the main eukaryotic single‐strand (ss) DNA‐binding involved in DNA replication and repair. We have identified developed two classes of small molecule inhibitors (SMIs) that show vitro inhibition RPA‐DNA interaction. present further characterization these SMIs with respect to their target binding, mechanism action, specificity. Both reversible irreversible modes are observed for different one class found specifically interact domains B (DBD‐A/B) RPA. In...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Facile Oxidation of Alcohols Using Pyridinium Chlorochromate/Silica GelFrederick A. Luzzio , Richard W. Fitch William J. Moore and Kelli Mudd View Author Information University Louisville, Department Chemistry, KY 40292Cite this: Chem. Educ. 1999, 76, 7, 974Publication Date (Web):July 1, 1999Publication History Received3 August 2009Published online1 July 1999Published inissue 1...
A phytochemical investigation of Abuta rufescens was performed to authenticate plant material reported previously and assess the cytotoxicity alkaloids obtained from plant. Three which have not been this species, two phenolic (subsessiline, an oxoaporphine, telitoxine, azafluoranthene) one non-phenolic (isoimerubrine, a tropoloisoquinoline), were isolated identified. These alkaloids, along with others another species (grandirubrine, evaluated for cytotoxic activity against several human...
Understanding the origins of novel, complex phenotypes is a major goal in evolutionary biology. Poison frogs family Dendrobatidae have evolved novel ability to acquire alkaloids from their diet for chemical defense at least three times. However, taxon sampling has been biased towards colorful species, without similar attention paid inconspicuous ones that are often assumed be undefended. As result, our understanding how this group incomplete. Here we provide new data showing that, contrast...
Phantasmidine, a rigid congener of the well-known nicotinic acetylcholine receptor agonist epibatidine, is found in same species poison frog (Epipedobates anthonyi). Natural phantasmidine was to be 4:1 scalemic mixture, enriched (2aR,4aS,9aS) enantiomer by chiral-phase LC-MS comparison synthetic enantiomers whose absolute configurations were previously established Mosher's amide analysis. The major has opposite S configuration at benzylic carbon natural R. Pharmacological characterization...
A microscale isotopic labeling experiment is described for the introductory organic chemistry laboratory course wherein half of students use sodium borohydride (NaBH4) and other borodeuteride (NaBD4) to reduce acetophenone 1-phenylethanol then compare spectral data. The cost reasonable, well-suited serve as a first experience with 1H NMR spectroscopy, infrared and/or mass spectrometry. No special apparatus are required reaction. entire experiment, including an extensive prelab lecture...
A kinetic isotope effect (KIE) experiment is described for the physical chemistry laboratory. Students conduct a hypochlorite (household bleach) oxidation of an equimolar mixture 1-phenylethanol and 1-deuterio-1-phenylethanol to acetophenone. The reaction occurs in biphasic follows first-order kinetics with respect either isotopomer 1-phenylethanol. Reaction progress measured by gas chromatography–mass spectrometry (GC–MS). Alternatively, could be conducted each serially followed GC alone....