Synthesis and biological evaluation of nigranoic acid esters as novel human neutrophil elastase inhibitors

被引：6
|
作者：
Huang, Guoli [1 ]
Feng, Li [2 ]
Liu, Bo [1 ]
He, Yi [2 ]
Li, Yiming [2 ]
Chen, Yegao [1 ]
机构：
[1] Yunnan Normal Univ, Sch Chem & Chem Engn, Kunming 650050, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China
来源：
NATURAL PRODUCT RESEARCH | 2015年 / 29卷 / 17期
关键词：
nigranoic acid esters; human neutrophil elastase; inhibition; TRITERPENOIDS; HYDROXYLATION; MECHANISM;
D O I：
10.1080/14786419.2014.996149
中图分类号：
O69 [应用化学];
学科分类号：
081704 ;
摘要：
Human neutrophil elastase (HNE) has been implicated as a major contributor in the pathogenesis of diseases, such as lung disorders and other inflammatory diseases. A series of 12 new nigranoic acid esters were regioselectively synthesised in good yields and evaluated for HNE inhibitory activity. Nigranoic acid exhibited significant inhibitory activity against HNE with the IC50 value of 3.77M, and six esters displayed considerable inhibitory effects on HNE with IC50 values in the range of 2.61-8.95M. The nigranoic acid esters having phenyls substituted with bromine and trimethoxyls (3h and 3b) showed stronger inhibitory activity on HNE than nigranoic acid.
引用
收藏
页码：1650 / 1656
页数：7
相关论文
共 50 条
  • [1] Synthesis and evaluation of benzenesulfonic acid derivatives as human neutrophil elastase (hNE) inhibitors
    Xu, Yanzhao
    Qi, Na
    Wen, Hui
    Zhang, Gang
    Wang, Yuchen
    Cui, Huaqing
    MEDICINAL CHEMISTRY RESEARCH, 2021, 30 (02) : 387 - 398
  • [2] Synthesis and evaluation of benzenesulfonic acid derivatives as human neutrophil elastase (hNE) inhibitors
    Yanzhao Xu
    Na Qi
    Hui Wen
    Gang Zhang
    Yuchen Wang
    Huaqing Cui
    Medicinal Chemistry Research, 2021, 30 : 387 - 398
  • [3] Synthesis, biological evaluation, and molecular modelling studies of potent human neutrophil elastase (HNE) inhibitors
    Giovannoni, Maria Paola
    Schepetkin, Igor A.
    Quinn, Mark T.
    Cantini, Niccolo
    Crocetti, Letizia
    Guerrini, Gabriella
    Iacovone, Antonella
    Paoli, Paola
    Rossi, Patrizia
    Bartolucci, Gianluca
    Menicatti, Marta
    Vergelli, Claudia
    JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2018, 33 (01) : 1108 - 1124
  • [4] Synthesis and Evaluation of Silanediols as Highly Selective Uncompetitive Inhibitors of Human Neutrophil Elastase
    Madsen, Julie L. H.
    Andersen, Thomas L.
    Santamaria, Salvatore
    Nagase, Hideaki
    Enghild, Jan J.
    Skrydstrup, Troels
    JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (17) : 7900 - 7908
  • [5] Structure based design, synthesis, and anticancer evaluation of human neutrophil elastase inhibitors
    Sun, Qi
    Li, Yong-Xin
    Li, Jun
    Yang, Wenchao
    Yang, Guang-Fu
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2015, 249
  • [6] Synthesis and evaluation of novel β-lactam inhibitors of human leukocyte elastase
    Koteva, K.P.
    Cantin, A.M.
    Neugebauer, W.A.
    Escher, E.
    2001, National Research Council of Canada (79)
  • [7] Human neutrophil elastase inhibitors
    Lloyd, AW
    DRUG DISCOVERY TODAY, 1997, 2 (04) : 162 - 162
  • [8] Inhibitors of human neutrophil elastase
    Edwards, PD
    Veale, CA
    EXPERT OPINION ON THERAPEUTIC PATENTS, 1997, 7 (01) : 17 - 28
  • [9] Design and synthesis of sirtinol analogs as human neutrophil elastase inhibitors
    Hwang, Tsong-Long
    Lin, Jing-Yi
    Kuo, Liang-Mou
    Dhandabani, Ganesh Kumar
    Hsieh, Pei-Wen
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2023, 97
  • [10] SYNTHESIS OF PEPTIDYL FLUOROMETHYL KETONES AND PEPTIDYL ALPHA-KETO ESTERS AS INHIBITORS OF PORCINE PANCREATIC ELASTASE, HUMAN NEUTROPHIL ELASTASE, AND RAT AND HUMAN NEUTROPHIL CATHEPSIN-G
    PEET, NP
    BURKHART, JP
    ANGELASTRO, MR
    GIROUX, EL
    MEHDI, S
    BEY, P
    KOLB, M
    NEISES, B
    SCHIRLIN, D
    JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (01) : 394 - 407
12345