Home Journals Articles Updates About
CN
image
收藏切换
Hybrid molecules of dihydroartemisinin with fluoroquinolones linked by L-homoserine have anti-tuberculosis and lipid-lowering effects
收藏切换
PDF
Jian-fang PAN1, Xiao-li SUN1, Li FAN1, Xue-mei TANG2, Peng LUO1, Da-cheng YANG1, *
Acta Pharmaceutica Sinica | 2020, 55(9) : 2157 - 2169
Less
收藏切换
Acta Pharmaceutica Sinica | 2020, 55(9): 2157-2169
• Original Articles •
Hybrid molecules of dihydroartemisinin with fluoroquinolones linked by L-homoserine have anti-tuberculosis and lipid-lowering effects
Full
Jian-fang PAN1, Xiao-li SUN1, Li FAN1, Xue-mei TANG2, Peng LUO1, Da-cheng YANG1, *
Affiliations
  • 1. Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic and Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China
  • 2. School of Life Science, Southwest University, Chongqing 400715, China
Published: 2020-09-12 doi: 10.16438/j.0513-4870.2020-0276
Outline
收藏切换

Eighteen dihydroartemisinin-fluoroquinolone molecules conjugated with L-homoserine were designed and synthesized using fragmented drug splicing approaches. The in vitro activities of the synthesized conjugates against Mycobacterium tuberculosis (MTB) and the lipid-lowering target PCSK9 were evaluated. The bioassay test results showed that most of the synthesized molecules had anti-tuberculosis (anti-TB) activity. Five compounds showed greater than 80% inhibitory activity against MTB in the replication state and three compounds exhibited more than 50% inhibitory activity against H37Rv in the non-replication state. A structure-activity relationship analysis demonstrated that TM2 series compounds (Boc protection) have better anti-TB activity than TM1 series compounds (Cbz protection). There were 13 compounds with strong inhibitory activity toward PCSK9 (>73%) and TM1-3 compounds reached 92%. The determination of physical parameters showed that all the molecules are largely nontoxic. The structure-toxicity relationship analysis showed that the safety of TM2 is higher than that of TM1 in all parameters, perhaps related to the protecting group of the amino acid in the target molecule, and provides new ideas for the design and structural modification of subsequent molecules. This study sets a precedent for L-homoserine as a linking structural unit in multi-target drug molecules.

dihydroartemisinin  /  fluoroquinolone  /  antituberculosis activity  /  PCSK9 inhibitory activity  /  L-homoserine
Jian-fang PAN, Xiao-li SUN, Li FAN, Xue-mei TANG, Peng LUO, Da-cheng YANG. Hybrid molecules of dihydroartemisinin with fluoroquinolones linked by L-homoserine have anti-tuberculosis and lipid-lowering effects[J]. Acta Pharmaceutica Sinica, 2020 , 55 (9) : 2157 -2169 . DOI: 10.16438/j.0513-4870.2020-0276
Appendix
Less
Year 2020 volume 55 Issue 9
PDF
196
83
Cite this Article
BibTeX
Article Info
doi: 10.16438/j.0513-4870.2020-0276
  • Receive Date：2020-03-10
  • Online Date：2026-01-23
  • Published：2020-09-12
Article Data
Affiliations
History
  • Received：2020-03-10
  • Revised：2020-04-04
Funding
Affiliations
    1. Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic and Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China
    2. School of Life Science, Southwest University, Chongqing 400715, China
References
Share
https://castjournals.cast.org.cn/joweb/yxxb/EN/10.16438/j.0513-4870.2020-0276
Share to
QR

Scan QR to access full text

Cite this article
BibTeX
Citations
表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
关闭全屏
  • BibTeX
  • EndNote
  • RefWorks
  • TxT
Links
Articles
Latest Articles
Most Read
Collections
Updates
Events
News
Multimedia
About
About Us
Contact
No. 86 Xueyuan South Road, Haidian District, Beijing
100081
010-62199257
qkjq@cast.org.cn

Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House