A5025355667- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Electrolyte and hormonal disorders
- Amino Acid Enzymes and Metabolism
- Malaria Research and Control
- Cystic Fibrosis Research Advances
- Synthesis and bioactivity of alkaloids
- Peptidase Inhibition and Analysis
- Nitric Oxide and Endothelin Effects
- Drug Transport and Resistance Mechanisms
- Adenosine and Purinergic Signaling
- Diet and metabolism studies
- Chemical Synthesis and Analysis
- Cancer therapeutics and mechanisms
- Radical Photochemical Reactions
- Computational Drug Discovery Methods
- Microwave-Assisted Synthesis and Applications
- Enzyme function and inhibition
- Neonatal Health and Biochemistry
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Metabolism, Diabetes, and Cancer
- Growth Hormone and Insulin-like Growth Factors
- Renin-Angiotensin System Studies
- Aldose Reductase and Taurine
San Francisco State University
2015-2024
University of North Carolina at Chapel Hill
2023
Lung Institute
2023
University of California, San Francisco
2005-2018
Yonsei University
2015
PharmChem (United States)
2005
University of California, Santa Cruz
1998-2002
Urea transporters, which include UT-B in kidney microvessels, are potential targets for development of drugs with a novel diuretic ('urearetic') mechanism. We recently identified, by high-throughput screening, triazolothienopyrimidine inhibitor, 1, that selectively and reversibly inhibited urea transport IC(50) = 25.1 nM reduced urinary concentration mice ( Yao et al. J. Am. Soc. Nephrol. , press ). Here, we analyzed 273 commercially available analogues 1 to establish structure-activity...
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of spinal cord and optic nerve caused by pathogenic autoantibodies (NMO-IgG) against astrocyte aquaporin-4 (AQP4). We developed a high-throughput screen to identify blockers NMO-IgG binding human AQP4 using recombinant monoclonal transfected Fisher rat thyroid cells stably expressing M23-AQP4. Screening ~60,000 compounds yielded the antiviral arbidol, flavonoid tamarixetin, several plant-derived berbamine alkaloids, each...
Abstract A microwave‐mediated Pictet–Spengler procedure utilizing 1,2‐dichloroethane (DCE) and trifluoroacetic acid (TFA) was developed to provide tetrahydro‐β‐carboline salts in high yields. Reactions are complete 20 minutes or less the product precipitates from solution yields purity, negating need for liquid–liquid extraction column chromatography. This method tolerates a wide range of functionality can be performed on milligram gram scales. subsequent aromatization synthesized...
Urea transport (UT) proteins facilitate the concentration of urine by kidney, suggesting that inhibition these could have therapeutic use as a diuretic strategy. We screened 100,000 compounds for UT-B using an optical assay based on hypotonic lysis acetamide-loaded mouse erythrocytes. identified class triazolothienopyrimidine inhibitors; most potent compound, UTB(inh)-14, fully and reversibly inhibited urea with IC(50) values 10 nM 25 human UT-B, respectively. UTB(inh)-14 competed binding at...
The emergence of artemisinin-resistant Plasmodium falciparum strains poses a serious challenge to the control malaria. This necessitates development new anti-malarial drugs. Previous studies have shown that natural beta-carboline alkaloid harmine is promising agent targeting P. heat-shock protein 90 (PfHsp90). aim this study was test activity analogues. Forty-two analogues were synthesized and binding these heat shock investigated. in vitro two analogues, 17A 21A, evaluated using 72-h growth...
Transmembrane protein 16A (TMEM16A), also called anoctamin 1 (ANO1), is a calcium-activated chloride channel expressed widely mammalian cells, including epithelia, vascular smooth muscle tissue, electrically excitable and some tumors. TMEM16A inhibitors have been proposed for treatment of disorders epithelial fluid mucus secretion, hypertension, asthma, possibly cancer. Herein we report, by screening, the discovery 2-acylaminocycloalkylthiophene-3-carboxylic acid arylamides (AACTs) as...
A library of diarylurea IGFR inhibitors was screened for activity against chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains Plasmodium falciparum. The 4-aminoquinaldine-derived diarylureas displayed promising antimalarial potency. Further exploration the B ring 4-aminoquinaldinyl ureas allowed identification several quinaldin-4-yl 4{13, 39} 58} sufficiently potent both 3D7 K1 to qualify as bone fide leads.
The aquaporin-1 (AQP1) water channel is a potentially important drug target, as AQP1 inhibition predicted to have therapeutic action in edema, tumor growth, glaucoma, and other conditions. Here, we measured the efficacy of 12 putative small-molecule inhibitors reported six recent studies, one activator. Osmotic permeability was by stopped-flow light scattering human rat erythrocytes that natively express AQP1, hemoglobin-free membrane vesicles from erythrocytes, plasma isolated...
Malaria remains one of the most deadly infectious diseases, causing hundreds thousands deaths each year, primarily in young children and pregnant mothers. Here, we report discovery derivatization a series pyrazolo[3,4-b]pyridines targeting Plasmodium falciparum, deadliest species malaria parasite. Hit compounds this display sub-micromolar vitro activity against intraerythrocytic stage parasite as well little to no toxicity human fibroblast BJ liver HepG2 cell lines. In addition, our hit show...
Herein we report a solid-phase synthetic approach to [Ala7]-phalloidin (1). Prior syntheses of phallotoxins were carried out using solution-phase routes that required large scale and preclude library production. The route presented here consists preparation key orthogonally protected amino acid building blocks, followed by peptide synthesis sequence, featuring two resin-bound macro-cyclization reactions. final product mixture was composed atropisomeric compounds, one designated "natural" (1)...