Design, synthesis and anti-inflammatory activity study of lansiumamide analogues for treatment of acute lung injury

Liyan Song; Gang Li; Wen Guan; Zhijun Zeng; Yanghui Ou; Tongchao Zhao; Jiayu Li; Dengqin He; Xiangxiang Fang; Yali Zhang; Jia-Qiang Wu; Rongbiao Tong; Hongliang Yao

doi:10.1016/j.biopha.2023.115412

Design, synthesis and anti-inflammatory activity study of lansiumamide analogues for treatment of acute lung injury

Biomed Pharmacother. 2023 Oct:166:115412. doi: 10.1016/j.biopha.2023.115412. Epub 2023 Sep 4.

Authors

Liyan Song¹, Gang Li², Wen Guan², Zhijun Zeng², Yanghui Ou², Tongchao Zhao¹, Jiayu Li², Dengqin He³, Xiangxiang Fang², Yali Zhang², Jia-Qiang Wu³, Rongbiao Tong⁴, Hongliang Yao⁵

Affiliations

¹ Key Laboratory of Biopesticide and Chemical Biology (Ministry of Education), College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China.
² Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China.
³ School of Biotechnology and Health Sciences, Wuyi University, 22 Dongchengcun, Jiangmen 529020, China.
⁴ Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China; Department of Chemistry, The Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong, China. Electronic address: rtong@ust.hk.
⁵ Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China. Electronic address: yaohl@giz.gd.cn.

PMID: 37660652
DOI: 10.1016/j.biopha.2023.115412

Abstract

Acute lung injury (ALI) is an inflammation-mediated respiratory disease with a high mortality rate. Medications with anti-inflammatory small molecules have been demonstrated in phase I and II clinical trials to considerably reduce the ALI mortality. In this study, two series of lansiumamide analogues were designed, synthesized, and evaluated for anti-inflammatory activity for ALI treatment. We found that compound 8n exhibited the best anti-inflammatory activity through inhibiting LPS-induced expression of the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-1β (IL-1β) in Raw264.7 cells and activating the Nrf2/HO-1 pathway. Furthermore, we discovered in a LPS-induced ALI mice model that compound 8n significantly reduced the infiltration of inflammatory cells into lung tissue to achieve the effect of protecting lung tissues and improving ALI. Additionally, our mice model study revealed that compound 8n had a good expectorant effect. These results consistently support that lansiumamide analogue 8n represents a new class of anti-inflammatory agents with potential as a lead compound for further development into a therapeutic drug for ALI treatment.

Keywords: ALI; Anti-inflammatory; Expectorant; Lansiumamide analogues; Nrf2/HO-1 pathway.

MeSH terms

Acute Lung Injury* / chemically induced
Acute Lung Injury* / drug therapy
Animals
Anti-Inflammatory Agents / pharmacology
Anti-Inflammatory Agents / therapeutic use
Cytokines
Disease Models, Animal
Inflammation
Lipopolysaccharides* / toxicity
Mice

Substances

Lipopolysaccharides
Anti-Inflammatory Agents
Cytokines