2. Academic Validation
  3. Discovery of novel Ebola entry inhibitors with 1,2,3,4-tetrahydroisoquinoline-3-carboxamide based on (3S,4aS,8aS)-2-(3-amino-2-hydroxypropyl) decahydroisoquinoline-3-carboxamide scaffold

Discovery of novel Ebola entry inhibitors with 1,2,3,4-tetrahydroisoquinoline-3-carboxamide based on (3S,4aS,8aS)-2-(3-amino-2-hydroxypropyl) decahydroisoquinoline-3-carboxamide scaffold

  • Bioorg Med Chem Lett. 2025 Aug 1:123:130230. doi: 10.1016/j.bmcl.2025.130230.
Junzhen Lin 1,  Fuling Xiao 2,  Sheng Han 3,  Youhong Hu 4,  Jianping Zuo 2,  Xiankun Tong 5,  Wuhong Chen 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Drug Research, 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.
  • 2 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 ZuChongZhi Road, Shanghai, 201203, China; Immunological Disease Research Center, 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.
  • 3 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 ZuChongZhi Road, Shanghai, 201203, China. Electronic address: hansheng8114593@163.com.
  • 4 State Key Laboratory of Drug Research, 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; School of Chinese Materia Medica, College of Pharmacy, Nanjing University of Chinese Medicine, No. 138 Xianlin Road, Nanjing, 210023, China; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1st Xiangshan Branch Alley, Hangzhou, 310024, China; Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong, 264117, China.
  • 5 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 ZuChongZhi Road, Shanghai, 201203, China; Immunological Disease Research Center, 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: xktong@simm.ac.cn.
  • 6 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 ZuChongZhi Road, Shanghai, 201203, China. Electronic address: whchen@simm.ac.cn.
PMID: 40199405 DOI: 10.1016/j.bmcl.2025.130230
Abstract

Novel Ebola entry inhibitors were designed and synthesized based on decahydroisoquinolines by streamlining non-essential functional groups that do not compromise activity. All novel derivatives were evaluated for their anti-Ebola activities and cytotoxicitiies in a defective Ebola virus model. A novel tetrahydroisoquinoline Ebola virus entry inhibitor, Hu7, was readily available with Antiviral activity comparable to previous findings, while demonstrating a marked reduction in toxicity. Such new compounds with simple and easy-to-synthesize structures could be potential leads for further optimizing the development of anti-Ebola drugs.

Keywords

Ebola virus entry inhibitor Tetrahydroisoquinoline.

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