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

• Published in: European journal of medicinal chemistry Vol. 156; pp. 618 - 627
• Main Authors: Liu, Qingbo, Li, Wei, Huang, Li, Asada, Yoshihisa, Morris-Natschke, Susan L., Chen, Chin-Ho, Lee, Kuo-Hsiung, Koike, Kazuo
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 05.08.2018; Elsevier
• Subjects: 3-(2-Naphthoyl)ingenol; Anti-HIV; Antiviral Agents - chemistry; Antiviral Agents - isolation & purification; Antiviral Agents - pharmacology; Cell Line; Chemistry, Medicinal; Diterpenes - chemistry; Diterpenes - isolation & purification; Diterpenes - pharmacology; Esters - chemistry; Esters - isolation & purification; Esters - pharmacology; Euphorbia - chemistry; Euphorbia kansui; HIV Infections - drug therapy; HIV-1 - drug effects; HIV-1 - physiology; Humans; Ingenane; Latency-reversing agent; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Science & Technology; Virus Replication - drug effects; Euphorbia kansui; 3-(2-Naphthoyl)ingenol; Anti-HIV; Ingenane; Latency-reversing agent; DITERPENES; ACTIVATION; ROOTS; ANTIRETROVIRAL THERAPY; LATENCY; EXPRESSION
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2018.07.020

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. [Display omitted] •MeOH extract of Euphorbia kansui showed potent anti-HIV-1 activity.•Ingenane esters from Euphorbia kansui are potent anti-HIV-1 agents.•Naphthoyl group at C-3 of 20-deoxyingenol and ingenol enhanced anti-HIV-1 activity.•3-(2-Naphthoyl)ingenol is a potent HIV-1 latency reversing agent.