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

Yi-Han Chang; Fang Shu-Yen; Hsuan-Yu Lai; Tsong-Long Hwang; Hsin-Yi Hung

doi:10.1016/j.bmcl.2021.127822

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. Epub 2021 Jan 27.

Authors

Yi-Han Chang¹, Fang Shu-Yen², Hsuan-Yu Lai¹, Tsong-Long Hwang³, Hsin-Yi Hung⁴

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: z10308005@email.ncku.edu.tw.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anions / antagonists & inhibitors
Anions / metabolism
Chromones / chemical synthesis
Chromones / chemistry
Chromones / pharmacology*
Dose-Response Relationship, Drug
Humans
Molecular Structure
Neutrophils / drug effects*
Neutrophils / metabolism
Structure-Activity Relationship
Superoxides / antagonists & inhibitors*
Superoxides / metabolism

Substances

Anions
Chromones
Superoxides