A5081706069- Inflammatory mediators and NSAID effects
- Estrogen and related hormone effects
- Cannabis and Cannabinoid Research
- Alcohol Consumption and Health Effects
- Microbial Natural Products and Biosynthesis
- Rheumatoid Arthritis Research and Therapies
- Immunotherapy and Immune Responses
- Steroid Chemistry and Biochemistry
- Synthesis and Biological Evaluation
- NF-κB Signaling Pathways
- Synthesis and biological activity
- Peroxisome Proliferator-Activated Receptors
- T-cell and B-cell Immunology
- Pharmacogenetics and Drug Metabolism
- Immune Response and Inflammation
- Fungal Biology and Applications
- Neonatal Health and Biochemistry
- Liver Disease Diagnosis and Treatment
- Cancer, Stress, Anesthesia, and Immune Response
- Forensic Toxicology and Drug Analysis
- Bioactive Compounds and Antitumor Agents
- Neuropeptides and Animal Physiology
- Erythrocyte Function and Pathophysiology
- Autophagy in Disease and Therapy
- Synthesis and Catalytic Reactions
Chinese University of Hong Kong, Shenzhen
2024
University of Chinese Academy of Sciences
2021-2024
Qilu Hospital of Shandong University
2024
Vanderbilt University
2012-2020
Anhui Medical University
2014-2019
Vanderbilt University Medical Center
2018
Ministry of Education of the People's Republic of China
2014-2015
Korea University Medical Center
2015
Institute of Chemical Biology and Fundamental Medicine
2014
University of Tennessee at Knoxville
2012
Chaetominine (1), an alkaloidal metabolite with a new framework, was characterized from the solid-substrate culture of Chaetomium sp. IFB-E015, endophytic fungus on apparently healthy Adenophora axilliflora leaves. Its structure determined by combination its spectral data and single-crystal X-ray diffraction analysis, absolute configuration elucidated Marfey's method. more cytotoxic than 5-fluorouracil against human leukemia K562 colon cancer SW1116 cell lines.
Oxicams are widely used nonsteroidal anti-inflammatory drugs (NSAIDs), but little is known about the molecular basis of interaction with their target enzymes, cyclooxygenases (COX). Isoxicam a nonselective inhibitor COX-1 and COX-2 whereas meloxicam displays some selectivity for COX-2. Here we report crystal complexes isoxicam at 2.0 2.45 angstroms, respectively, complex 2.4 angstroms. These structures reveal that oxicams bind to active site using binding pose not seen other NSAIDs through...
Abstract Carbaboranes are increasingly studied as pharmacophores, particularly replacements for aromatic systems. However, especially ortho ‐carbaborane is prone to degradation of the cluster, which hampers biological application. This study demonstrates that deboronation cluster may not only lead a more active analogue, but can also improve solubility and stability carbaborane‐containing inhibitor. Notably, introduction nido ‐dicarbaborate into cyclooxygenase (COX) inhibitor indomethacin...
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic and continues to rise in worldwide. Limonin a triterpenoid compound widely found fruits citrus plants with wide range pharmacological effects, including anti-cancer, anti-inflammation, anti-viral, anti-oxidation protection properties. However, potential molecular mechanism limonin on NAFLD zebrafish remains unknown. In this study, larvae were exposed thioacetamide establish an model treated for 72 h simultaneously....
Cyclooxygenase enzymes (COX-1 and COX-2) catalyze the conversion of arachidonic acid to prostaglandin G2. The inhibitory activity rapid, reversible COX inhibitors (ibuprofen, naproxen, mefenamic acid, lumiracoxib) demonstrated a significant increase in potency time dependence inhibition against double tryptophan murine COX-2 mutants at 89/90 89/119 positions. In contrast, slow, time-dependent (diclofenac, indomethacin, flurbiprofen) were unaffected by those mutations. Further mutagenesis...
Lysophospholipids (LysoPLs) are bioactive lipid species involved in cellular signaling processes and the regulation of cell membrane structure. LysoPLs metabolized through action lysophospholipases, including lysophospholipase A1 (LYPLA1) A2 (LYPLA2). A new X-ray crystal structure LYPLA2 compared with a previously published LYPLA1 demonstrated near-identical folding two enzymes; however, have displayed distinct substrate specificities recombinant enzyme assays. To determine how these vitro...
Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid and the endocannabinoids 2-arachidonoylglycerol (2-AG) arachidonoylethanolamide (AEA). We recently reported that (R)-profens selectively inhibit endocannabinoid oxygenation but not oxygenation. In this work, we synthesized achiral derivatives of five profen scaffolds evaluated them for substrate-selective inhibition using in vitro cellular assays. The size substituents dictated inhibitory strength analogs, with smaller enabling greater...
Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid (AA) and the endocannabinoids 2-arachidonoylglycerol (2-AG) arachidonylethanolamide to prostaglandins, prostaglandin glyceryl esters, ethanolamides, respectively. A structural homodimer, COX-2 acts as a conformational heterodimer with catalytic an allosteric monomer. Prior studies have demonstrated substrate-selective negative regulation of 2-AG oxygenation. Here we describe AM-8138 (13(S)-methylarachidonic acid), potentiator that augments...
Many indomethacin amides and esters are cyclooxygenase-2 (COX-2)-selective inhibitors, providing a framework for the design of COX-2-targeted imaging cancer chemotherapeutic agents. Although previous studies have suggested that amide or ester moiety these inhibitors binds in lobby region, spacious alcove within enzyme's membrane-binding domain, structural details been lacking. Here, we present observations on crystal complexes COX-2 with two indomethacin-dansyl conjugates (compounds 1 2) at...
High cyclooxygenase (COX)-2 expression in ovarian tumors has been associated with poor prognosis, but the role of COX-1 and its relation to survival is less clear. Here, we evaluated COX associations outcomes between type I (clear cell, mucinous, low grade endometrioid serous) II (high serous high endometrioid) tumors.
Binding of the thiazolidinedione antidiabetic drug pioglitazone led to discovery a novel outer mitochondrial membrane protein unknown function called mitoNEET. The is homodimeric and contains uniquely ligated two iron–two sulfur cluster in each its cytosolic domains. Electrospray ionization mass spectrometry was employed characterize solutions soluble domain (amino acids 32–108) protein. Ions characteristic dimers containing cofactors were readily detected under native conditions. mitoNEET...
Oxidative stress is a contributing factor in number of chronic diseases, including cancer, atherosclerosis, and neurodegenerative diseases. Lipid peroxidation that occurs during periods oxidative results the formation lipid electrophiles, which can modify multitude proteins cell. 4-Hydroxy-2-nonenal (HNE) one most well-studied electrophiles has previously been shown to arrest cells at G1/S transition. Recently, proteomic data have HNE capable covalently modifying CDK2, kinase responsible for...
Targeted delivery of chemotherapeutic agents to tumors has been explored as a means increase the selectivity and potency cytotoxicity. Most efforts in this area have exploited molecular recognition proteins highly expressed on surface cancer cells followed by internalization. A related approach that received less attention is targeting intracellular ligands conjugated anticancer drugs. An attractive target for enzyme cyclooxygenase-2 (COX-2), which range malignant tumors. Herein, we describe...
We report the design, synthesis, and evaluation of a series harmaline analogs as selective inhibitors 2-arachidonylglycerol (2-AG) oxygenation over arachidonic acid (AA) by purified cyclooxygenase-2 (COX-2). A fused tricyclic analog containing CH3O substituent at C-6 CH3 group C-1 position 4,9-dihydro-3H-pyrido[3,4-b]indole (compound 3) was best substrate-selective COX-2 inhibitor those evaluated, exhibiting 2AG-selective inhibitory IC50 0.022 μM compared to >1 for AA. The 2.66 Å resolution...
Abstract magnified image In addition to the known metabolites cytochalasin H ( 1 ), J 2 and epoxycytochalasin 3 two new 10‐phenyl‐(11)‐cytochalasans, named Z10 Z11 4 5 , resp.) were isolated from solid substrate culture of Endothia gyrosa IFB‐E023, an endophytic fungus residing inside healthy leaf Vatica mangachapo (Dipterocarpaceae). The structure determination was accomplished through correlative analyses their spectral data (UV, ESI‐MS, IR, H‐ 13 C‐NMR, COSY, NOESY, HMQC, HMBC)....
Lumiracoxib is a substrate-selective inhibitor of endocannabinoid oxygenation by cyclooxygenase-2 (COX-2). We assayed series lumiracoxib derivatives to identify the structural determinants inhibition. The hydrogen-bonding potential substituents at ortho positions aniline ring dictated potency and substrate selectivity inhibitors. presence 5′-methyl group on phenylacetic acid increased molecules with single substituent. Des-fluorolumiracoxib (2) was most potent selective oxygenation....