Betulin-derived compounds as inhibitors of alphavirus replication

L. Pohjala, Sami Alakurtti, T. Ahola, Jari Yli-Kauhaluoma, P. Tammela (Corresponding Author)

    Research output: Contribution to journalArticleScientificpeer-review

    74 Citations (Scopus)

    Abstract

    This paper describes inhibition of Semliki Forest virus (SFV) replication by synthetic derivatives of naturally occurring triterpenoid betulin (1). Chemical modifications were made to OH groups at C-3 and C-28 and to the C-20−C-29 double bond. A set of heterocyclic betulin derivatives was also assayed. A free or acetylated OH group at C-3 was identified as an important structural contributor for anti-SFV activity, 3,28-di-O-acetylbetulin (4) being the most potent derivative (IC50 value 9.1 μM). Betulinic acid (13), 28-O-tetrahydropyranylbetulin (17), and a triazolidine derivative (41) were also shown to inhibit Sindbis virus, with IC50 values of 0.5, 1.9, and 6.1 μM, respectively. The latter three compounds also had significant synergistic effects against SFV when combined with 3′-amino-3′-deoxyadenosine. In contrast to previous work on other viruses, the antiviral activity of 13 was mapped to take place in virus replication phase. The efficacy was also shown to be independent of external guanosine supplementation.
    Original languageEnglish
    Pages (from-to)1917-1926
    Number of pages10
    JournalJournal of Natural Products
    Volume72
    Issue number11
    DOIs
    Publication statusPublished - 2009
    MoE publication typeA1 Journal article-refereed

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