Abstract
Various bioisosteres of ethyl pyruvate (EP), where the oxygen atom in the ethoxy group was replaced by the corresponding bioisosteric atom such as carbon, nitrogen, and sulfur atoms, were synthesized and their inhibitory effects were tested for nitric oxide (NO) production and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-induced BV2 cells. The synthesized compounds generally revealed better activity than EP. Especially, the thio-bioisostere 4c (IC50 = 3.6 µM) exhibited a potency about 4.5 times greater than that of EP (IC50 = 16.1 µM) and suppressed NO production dose-dependently without cytotoxicity. Compound 4c also inhibited iNOS expression in LPS-induced BV2 cells at 1 µM and 10 µM concentrations. These results suggested that the ethoxy group in EP is not essential for the suppression of NO production and that 4c has potential as a potent inhibitor of NO production.
Keywords: Ethyl pyruvate, bioisosteres, microglia, BV2 cell, nitric oxide, inhibitor.
Letters in Drug Design & Discovery
Title:Syntheses of Ethyl Pyruvate’s Bioisosteres Inhibiting Inducible Nitric Oxide Production in Lipopolysaccharide-induced BV2 Cells
Volume: 12 Issue: 7
Author(s): Ju-Young Park, Byung-Wook Kim, Soon-Jung Kwon, Dong-Kug Choi, Ja-Kyeong Lee and Sung-Hwa Yoon
Affiliation:
Keywords: Ethyl pyruvate, bioisosteres, microglia, BV2 cell, nitric oxide, inhibitor.
Abstract: Various bioisosteres of ethyl pyruvate (EP), where the oxygen atom in the ethoxy group was replaced by the corresponding bioisosteric atom such as carbon, nitrogen, and sulfur atoms, were synthesized and their inhibitory effects were tested for nitric oxide (NO) production and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-induced BV2 cells. The synthesized compounds generally revealed better activity than EP. Especially, the thio-bioisostere 4c (IC50 = 3.6 µM) exhibited a potency about 4.5 times greater than that of EP (IC50 = 16.1 µM) and suppressed NO production dose-dependently without cytotoxicity. Compound 4c also inhibited iNOS expression in LPS-induced BV2 cells at 1 µM and 10 µM concentrations. These results suggested that the ethoxy group in EP is not essential for the suppression of NO production and that 4c has potential as a potent inhibitor of NO production.
Export Options
About this article
Cite this article as:
Park Ju-Young, Kim Byung-Wook, Kwon Soon-Jung, Choi Dong-Kug, Lee Ja-Kyeong and Yoon Sung-Hwa, Syntheses of Ethyl Pyruvate’s Bioisosteres Inhibiting Inducible Nitric Oxide Production in Lipopolysaccharide-induced BV2 Cells, Letters in Drug Design & Discovery 2015; 12 (7) . https://dx.doi.org/10.2174/1570180812999150225112225
DOI https://dx.doi.org/10.2174/1570180812999150225112225 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Virulence on the Fly: Drosophila melanogaster as a Model Genetic Organism to Decipher Host-Pathogen Interactions
Current Drug Targets Systems Biology of Apoptosis and Survival: Implications for Drug Development
Current Pharmaceutical Design Viral Induced Oxidative and Inflammatory Response in Alzheimer’s Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach
Current Neuropharmacology The Role of Viruses in Neurodegenerative and Neurobehavioral Diseases
CNS & Neurological Disorders - Drug Targets Sirtuin3 in Neurological Disorders
Current Drug Research Reviews Role of Free Radicals and Antioxidant Signaling in Skeletal Muscle Health and Pathology
Infectious Disorders - Drug Targets Evaluation of Venom as a Promising Tool for Drug Discovery: Focusing on Neurological Disorders
Venoms and Toxins Anti-IL-1 β Therapies
Recent Patents on DNA & Gene Sequences Oxidative Stress During Myocardial Ischaemia and Heart Failure
Current Pharmaceutical Design A New Risk Chart of Acute Myocardial Infarction in Men by an Innovative Algorithm: A Pilot Study
Current Pharmacogenomics and Personalized Medicine Relevance of Bioassay of Biologically Active Substances (BAS) with Geroprotective Properties in the Model of the Nematode <i>Caenorhabditis Elegans</i> in <i>In Vivo</i> Experiments
Current Aging Science Genetic Variants in Diseases of the Extrapyramidal System
Current Genomics GABAergic Pharmacotherapy in the Treatment of Motor Disorders of the Central Nervous System
Current Pharmaceutical Design Multi- and Inter-Disciplinary Science in Personalized Delivery of Stem Cells for Tissue Repair
Current Stem Cell Research & Therapy Integrated Analysis of Transcriptomic and Proteomic Data
Current Genomics Dynamic Expression of MicroRNAs (183, 135a, 125b, 128, 30c and 27a) in the Rat Pilocarpine Model and Temporal Lobe Epilepsy Patients
CNS & Neurological Disorders - Drug Targets Literature Evidence and ARRIVE Assessment on Neuroprotective Effects of Flavonols in Neurodegenerative Diseases' Models
CNS & Neurological Disorders - Drug Targets Nanoemulsions for Intranasal Delivery of Riluzole to Improve Brain Bioavailability: Formulation Development and Pharmacokinetic Studies
Current Drug Delivery Recent Advances in Health Promoting Effect of Dietary Polyphenols
Current Nutrition & Food Science Neurofilament Proteins as Prognostic Biomarkers in Neurological Disorders
Current Pharmaceutical Design