2. Academic Validation
  3. The study on structure-activity relationship between chromone derivatives and inhibition of superoxide anion generating from human neutrophils

The study on structure-activity relationship between chromone derivatives and inhibition of superoxide anion generating from human neutrophils

  • Bioorg Med Chem Lett. 2021 Mar 15:36:127822. doi: 10.1016/j.bmcl.2021.127822.
Yi-Han Chang 1,  Fang Shu-Yen 2,  Hsuan-Yu Lai 1,  Tsong-Long Hwang 3,  Hsin-Yi Hung 4
Affiliations

Affiliations

  • 1 School of Pharmacy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, ROC.
  • 2 Graduate Institute of Biomedical Sciences and Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, ROC.
  • 3 Graduate Institute of Biomedical Sciences and Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, ROC; Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan, ROC; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan, ROC.
  • 4 School of Pharmacy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, ROC. Electronic address: [email protected].
PMID: 33508463 DOI: 10.1016/j.bmcl.2021.127822
Abstract

Over activation of neutrophils has been linked to many inflammatory diseases; one of critical pathologic mechanisms is that generation and exocellular release of superoxide anion from neutrophils results in peripheral tissues damage. Besides, in this study, 2-(3,5-dimethoxyphenoxy)-5,7-dimethoxy-chromen-4-one (4), a 2-phexnoychromone from our compound bank, was demonstrated to have the moderate inhibitory effect on superoxide anion generating. Therefore, serial chromones substituted with Phenols or 3-flourothiophenol were designed, synthesized, and examined for suppression of superoxide anion generation. In accordance with the results, the methoxy group at 7 position (R3) of the chromone, as well as a hydrogen bond donor at a meta site of the phenyl ring greatly impacted on the activity. 2-(3-fluorophenyl)sulfanyl-7-methoxy-chromen-4-one (16), a successful example of bioisosteres from a phenol to a thiophenol, exhibited prominent anti-inflammatory effects with the IC50 value against superoxide anion generation of 5.0 ± 1.4 μM.

Keywords

2-Phenxoychromone; Inflammatory diseases; Neutrophils; Structure-activity relationship; Superoxide anion.

Figures