Triterpene derivatives that inhibit human immunodeficiency virus type 1 replication

University of Minnesota, Institute for Molecular Virology, 18-242 Moos Tower, 525 Delaware St SE, Minneapolis, MN 55455, United States.
Bioorganic & medicinal chemistry letters (Impact Factor: 2.42). 11/2010; 21(1):542-5. DOI: 10.1016/j.bmcl.2010.10.078
Source: PubMed


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.

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Available from: Louis M Mansky, Aug 25, 2014
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    • "Water (50 mL) and diluted aqueous hydrochloric acid (1 N) were added until the aqueous layer showed pH ¼ 7. The layers were separated, the aqueous layer was extracted with DCM (3 Â 50 mL), the combined organic phases were dried (Na 2 SO 4 ), and the solvent was distilled off under reduced pressure. The crude product was purified by chromatography (silica gel, hexanes/ethyl acetate, 7:3) to yield 19 (3.8 g, 95%) as a colorless solid; R F ¼ 0.12 (silica gel, hexanes/ethyl acetate, 8:2); m.p.: 336e338 C (lit.: [60] 340e341 C); [a] D ¼ þ17.0 (c ¼ 0.48, CHCl 3 ); IR (KBr): n ¼ 3471m, 3325m, 3202w, 3074w, 2940s, 2868m, 1742s, 1686s, 1642s, 1610m, 1449w, 1392m, 1367s, 1301w, 1242s, 1139w, 1108w, 1082w, 1025m, 1009m, 979m, 946w, 899w, 875m, 738w, 655w, 608w, 579w, 558w, 541w, 516w cm À1 ; 1 H NMR (400 MHz, CDCl 3 ): "
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    ABSTRACT: The betulinic acid-derived hydroxamates 5-18, the amides 19-24, and betulin-derived bis-carbamates 25-28 as well as the carbamates 31-40 and 44-48 were prepared and evaluated for their antiproliferative activity in a photometric sulforhodamine B (SRB) assay against several human cancer cell lines and nonmalignant mouse fibroblasts (NIH 3T3). While for 3-O-acetyl hydroxamic acid 5 EC50 values as low as EC50 = 1.3 μM were found, N,O-bis-alkyl substituted hydroxamates showed lowered cytotoxicity (EC50 = 16-20 μM). In general, hydroxamic acid derivatives showed only reduced selectivity for tumor cells, except for allyl substituted compound 13 (EC50 = 5.9 μM for A2780 human ovarian carcinoma cells and EC50 > 30 μM for nonmalignant mouse fibroblasts). The cytotoxicity of betulinic acid derived amides 19-24 and of betulin derived bis-carbamates 25-28 was low, except for N-ethyl substituted 25. Hexyl substituted 39 showed EC50 = 5.6 μM (518A2 cells) while for mouse fibroblasts EC50 > 30 was determined.
    Full-text · Article · Nov 2015 · European Journal of Medicinal Chemistry
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    • "Several triterpenoids containing a nitrogen atom on C-28 have shown significant biological activities [37] [38]. On this basis, we prepared a new series of MA derivatives with a nitrogen atom on C- 28, starting from this natural product (Scheme 2). "
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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.
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