Synthesis and biological evaluation of artemisinin derivatives as potential MS agents

Yan Zhang; Jie Lv; Suqing Zhang; Hanxi Yang; Jingshan Shen; Changsheng Du; Xiangrui Jiang; Haji A Aisa

doi:10.1016/j.bmcl.2022.128682

Synthesis and biological evaluation of artemisinin derivatives as potential MS agents

Bioorg Med Chem Lett. 2022 May 15:64:128682. doi: 10.1016/j.bmcl.2022.128682. Epub 2022 Mar 15.

Authors

Yan Zhang¹, Jie Lv², Suqing Zhang³, Hanxi Yang⁴, Jingshan Shen⁵, Changsheng Du⁶, Xiangrui Jiang⁷, Haji A Aisa⁸

Affiliations

¹ State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, and Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Road 40-1, Urumqi 830011, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
² Putuo People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
³ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
⁴ College of Chemistry, Zhengzhou University, 100 Kexuedadao Road, Zhengzhou 450001, China.
⁵ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
⁶ Putuo People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: duchangsheng@tongji.edu.cn.
⁷ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China. Electronic address: jiangxiangrui@simm.ac.cn.
⁸ State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, and Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Road 40-1, Urumqi 830011, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China. Electronic address: haji@ms.xjb.ac.cn.

PMID: 35304225
DOI: 10.1016/j.bmcl.2022.128682

Abstract

In this paper, a series of artemisinin derivatives were synthesized and evaluated. Studies have shown that IFN-γ produced by Th1 CD4⁺ T cells and IL-17A secreted by Th17 CD4⁺ T cells played critical roles in the treatment of multiple sclerosis. We used different concentrations of artemisinin derivatives to inhibit Th1 / Th17 differentiation in naive CD4⁺ T cells and to characterize IFN-γ / IL-17A in in vitro experiments. The preliminary screening results showed that ester compound 5 exhibited obvious inhibitory activities on Th1 and Th17 (IFN-γ decreased from 41% to 3% and IL-17A decreased from 24% to 8% at the concentration of 10 nM to 10 μM), and carbamate compounds also had obvious inhibitory activities against Th17 at high concentration. Moreover, we investigated the effect of compound 5 on myelin oligodendrocyte glycoprotein (MOG)-induced mice experimental autoimmune encephalomyelitis (EAE) model in vivo. 100 mg/kg compound 5 effectively reduced the disease severity of EAE compared with the vehicle group. This research revealed that compound 5 could be a promising avenue as potential MS inhibitor.

Keywords: Artemisinin derivatives; EAE; IFN-γ/IL-17A; Multiple sclerosis; Th1/Th17.

Publication types

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

MeSH terms

Animals
Artemisinins* / pharmacology
Cytokines
Encephalomyelitis, Autoimmune, Experimental* / drug therapy
Mice
Mice, Inbred C57BL
Th1 Cells
Th17 Cells

Substances

Artemisinins
Cytokines