Triterpene derivatives that inhibit human immunodeficiency virus type 1 replication
ABSTRACT Triterpene derivatives were analyzed for anti-HIV-1 activity and for cellular toxicity. Betulinic aldehyde, betulinic nitrile, and morolic acid derivatives were identified to have anti-HIV-1 activity. These derivatives inhibit a late step in virus replication, likely virus maturation.
Full-textDOI: · Available from: Louis M Mansky, Aug 25, 2014
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ABSTRACT: Maslinic acid (2α,3β-dihydroxyolean-12-en-28-oic acid), a natural dihydroxylated pentacyclic triterpene acid isolated from olive-pressing residues, has been investigated together with some of its derivatives regarding the induction of apoptosis in B16F10 melanoma cells. Some of the compounds tested are described in this work, but others come from previous studies. Ten of these derivatives induce over 80% of apoptosis, clearly promoting cell death in B16F10 melanoma. By contrast, the induction cell death through necrosis was very slightly significant with these compounds. These results indicate that maslinic acid derivatives are promising chemopreventive and chemotherapeutic agents.European Journal of Medicinal Chemistry 12/2011; 46(12):5991-6001. DOI:10.1016/j.ejmech.2011.10.011 · 3.43 Impact Factor
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ABSTRACT: The HIV-1 auxiliary protein Vpr and Vpr-fusion proteins can be copackaged with Gag precursor (Pr55Gag) into virions or membrane-enveloped virus-like particles (VLP). Taking advantage of this property, we developed a simple and sensitive method to evaluate potential inhibitors of HIV-1 assembly in a living cell system. Two proteins were coexpressed in recombinant baculovirus-infected Sf9 cells, Pr55Gag, which formed the VLP backbone, and luciferase fused to the N-terminus of Vpr (LucVpr). VLP-encapsidated LucVpr retained the enzymatic activity of free luciferase. The levels of luciferase activity present in the pelletable fraction recovered from the culture medium correlated with the amounts of extracellular VLP released by Sf9 cells assayed by conventional immunological methods. Our luciferase-based assay was then applied to the characterization of betulinic acid (BA) derivatives that differed from the leader compound PA-457 (or DSB) by their substituant on carbon-28. The beta-alanine-conjugated and lysine-conjugated DSB could not be evaluated for their antiviral potentials due to their high cytotoxicity, whereas two other compounds with a lesser cytotoxicity, glycine-conjugated and ε-NH-Boc-lysine-conjugated DSB, exerted a dose-dependent negative effect on VLP assembly and budding. A fifth compound with a low cytotoxicity, EP-39 (ethylene diamine-conjugated DSB), showed a novel type of antiviral effect. EP-39 provoked an aberrant assembly of VLP, resulting in nonenveloped, morula-like particles of 100-nm in diameter. Each morula was composed of nanoparticle subunits of 20-nm in diameter, which possibly mimicked transient intermediates of the HIV-1 Gag assembly process. Chemical cross-linking in situ suggested that EP-39 favored the formation or/and persistence of Pr55Gag trimers over other oligomeric species. EP-39 showed a novel type of negative effect on HIV-1 assembly, targeting the Pr55Gag oligomerisation. The biological effect of EP-39 underlined the critical role of the nature of the side chain at position 28 of BA derivatives in their anti-HIV-1 activity.PLoS ONE 11/2011; 6(11):e27234. DOI:10.1371/journal.pone.0027234 · 3.53 Impact Factor
- Value in Health 11/2008; 11(6). DOI:10.1016/S1098-3015(10)66811-8 · 2.89 Impact Factor