2. Academic Validation
  3. Identification, structural modification, and dichotomous effects on human immunodeficiency virus type 1 (HIV-1) replication of ingenane esters from Euphorbia kansui

Identification, structural modification, and dichotomous effects on human immunodeficiency virus type 1 (HIV-1) replication of ingenane esters from Euphorbia kansui

  • Eur J Med Chem. 2018 Aug 5:156:618-627. doi: 10.1016/j.ejmech.2018.07.020.
Qingbo Liu 1,  Wei Li 2,  Li Huang 3,  Yoshihisa Asada 4,  Susan L Morris-Natschke 5,  Chin-Ho Chen 6,  Kuo-Hsiung Lee 7,  Kazuo Koike 8
Affiliations

Affiliations

  • 1 Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba, 274-8510, Japan; Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China.
  • 2 Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba, 274-8510, Japan. Electronic address: [email protected].
  • 3 Surgical Science, Department of Surgery, Duke University Medical Center, Durham, NC, 27710, United States.
  • 4 Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba, 274-8510, Japan.
  • 5 Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, United States.
  • 6 Surgical Science, Department of Surgery, Duke University Medical Center, Durham, NC, 27710, United States. Electronic address: [email protected].
  • 7 Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, United States; Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, 40402, Taiwan. Electronic address: [email protected].
  • 8 Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba, 274-8510, Japan. Electronic address: [email protected].
PMID: 30031972 DOI: 10.1016/j.ejmech.2018.07.020
Abstract

Euphorbia kansui showed potent anti-HIV-1 activity during screening of a library composed of plant extracts from Euphorbiaceae and Thymelaeaceae families. Bioassay-guided isolation led to identification of ingenane esters as the active compounds. Further chemical modification resulted in 3-(2-naphthoyl)ingenol (23), which exhibited the most potent anti-HIV-1 activity. Compound 23 also acted as an HIV-1-latency-reversing agent on activation of HIV-1 replication in a latently infected U1 cell model and a T cell latent HIV-1 model JLat-A2.

Keywords

3-(2-Naphthoyl)ingenol; Anti-HIV; Euphorbia kansui; Ingenane; Latency-reversing agent.

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