Betulinic Acid Derivatives:  A New Class of Specific Inhibitors of Human Immunodeficiency Virus Type 1 Entry

Soler, F; Poujade, C.; Evers, M.; Carry, Jean‐Christophe; Hénin, Y.; Bousseau, A.; Huet, Thierry; Pauwels, Rudi; Clercq, Erik De; Mayaux, Jean‐François; Pecq, J.‐B. Le; Dereu, N.

doi:10.1021/jm950669u

Cited by 126 publications

(116 citation statements)

References 22 publications

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“…Derivatives (12,18,19,21 and 25) that showed the best antileishmanial activity on microplate assay at 50 mM against L. donovani axenic amastigotes were selected for further investigations: GI 50 values, cytotoxicity to the macrophage cell line THP-1 and anti-leishmanial activity against the L. donovani-infected macrophage cell line THP-1 were evaluated. Betulonic acid 18 showed the best GI 50 value of 14.6 mM on microplate assay against L. donovani axenic amastigotes, followed by L-aspartyl amide derivative 21 and oxime derivative 25, with GI 50 values of 21.2 and 22.8 mM, respectively (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…9,10 Some betulin derivatives have also shown remarkable anti-human immunodeficiency virus activity with new mechanisms of action. 11,12 Structure-activity relationship studies and pharmacological properties of betulin and its derivatives have been reviewed recently. 13 Previously, dihydrobetulinic acid 3 was examined as a new lead compound for anti-leishmanial therapy.…”

Section: Introductionmentioning

confidence: 99%

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Anti-leishmanial activity of betulin derivatives

et al. 2010

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Leishmanicidal activity of 24 derivatives of naturally occurring and abundant triterpenes belonging to the lupane series, betulin, betulinic acid and betulonic acid, is described in this study. The easily modified positions of the lupane skeleton, the hydroxy groups of C-3 and C-28, as well as the carbon-carbon double bond C-20-C-29 were used as a starting point to prepare a library of triterpenoid derivatives for bioactivity studies. The compounds were evaluated against Leishmania donovani axenic amastigotes on a microplate assay at 50 lM. GI 50 values of the most effective compounds were evaluated, as well as their cytotoxicity on the human macrophage cell line THP-1, and anti-leishmanial activity against L. donovani-infected THP-1 macrophages was determined. Betulonic acid was the most potent derivative, yielding a GI 50 value of 14.6 lM. Promising and distinct structure-activity relationships were observed, and these compounds can be regarded as significant lead molecules for further improvement and optimization.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti-leishmanial activity of betulin derivatives

et al. 2010

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“…Moreover, betulinic acid derivatives were able to block efficiently syncyticum formation of CD4 cells mediated by the HIV-1 envelope glycoproteins, which confirm the interaction of these substances with the post-binding viruscell fusion process (115).…”

Section: Terpenesmentioning

confidence: 52%

Untitled

2007

Planta Med

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Many compounds of plant origin have been identified that inhibit different stages in the replication cycle of human immunodeficiency virus (HIV): 1) virus adsorption: chromone alkaloids (schumannificine), isoquinoline alkaloids (michellamines), sulphated polysaccharides and polyphenolics, flavonoids, coumarins (glycocoumarin, licopyranocoumarin) phenolics (caffeic acid derivatives, galloyl acid derivatives, catechinic acid derivatives), tannins and triterpenes (glycyrrhizin and analogues, soyasaponin and analogues); 2) virus-cell fusion: lectins (mannose-and N-acetylglucosamine-specific) and triterpenes (betulinic acid and analogues); 3) reverse transcription: alkaloids (benzophenanthridines, protoberberines, isoquinolines, quinolines), coumarins (calanolides and analogues), flavonoids, phloroglucinols, lactones (protolichesterinic acid), tannins, indoids (fulvoplumierin) and triterpenes; 4) integration: coumarins (3-substituted-4-hydroxycoumarins), depsidones, O-caffeoyl derivatives, lignans (anctigenin and analogues) and phenolics (curcumin); 5) translation: single chain ribosome inactivating proteins (SCRIP's); 6) proteolytic cleavage (protease inhibition):saponins (ursolic and maslinic acids), xanthones (mangostin and analogues) and coumarins; 7) glycosylation: alkaloids including indolizidines (castanospermine and analogues), piperidines (1-deoxynojirimicin and analogues) and pyrrolizidines (australine and analogues); 8) assembly/release: naphthodianthrones (hypericin and pseudohypericin), photosensitisers (terthiophenes and furoisocoumarins) and phospholipids. The target of action of several anti-HIV substances including alkaloids (O-demethyl-buchenavianine, papaverine), polysaccharides (acemannan), lignans (intheriotherins, schisantherin), phenolics (gossypol, lignins, catechol dimers such as peltatols, naphthoquinones such as conocurvone) and saponins (celasdin B, Gleditsia and Gymnocladus saponins), has not been elucidated or does not fit in the proposed scheme. Only a very few of these plant-derived anti-HIV products have been used in a limited number of patients suffering from AIDS viz. glycyrrhizin, papaverine, trichosanthin, castanospermine, N-butyl-1 -deoxynojirirnicin and acemannan.

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“…Betulinic acid, a pentacyclic terterpene, and its derivatives have been reported to possess a variety of biological properties (Yogeeswari and Sriram, 2005) (Soler et al, 1996), anti-bacterial, anti-cancer (Chintharlapalli et al, 2007;Fulda, 2008), and anti-infl ammatory activities (Recio et al, 1995). Although anti-HIV and anti-cancer activities of betulinic acid and its derivatives have been reported to be through the inhibition of HIV entry, HIV-proteases or reverse transcriptase (Fujioka et al, 1994;Yogeeswari and Sriram, 2005), and through increased degradation of the transcription factors specifi city protein 1 (Sp1), Sp3, and Sp4 (Chintharlapalli et al, 2007), respectively, the underlying mechanism of anti-infl ammatory property of betulinic acid has not been clearly demonstrated (Recio et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Betulinic Acid Inhibits LPS-Induced MMP-9 Expression by Suppressing NF-kB Activation in BV2 Microglial Cells

Kim

2011

Biomolecules and Therapeutics

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Betulinic Acid Derivatives: A New Class of Specific Inhibitors of Human Immunodeficiency Virus Type 1 Entry

Cited by 126 publications

References 22 publications

Anti-leishmanial activity of betulin derivatives

Anti-leishmanial activity of betulin derivatives

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Betulinic Acid Inhibits LPS-Induced MMP-9 Expression by Suppressing NF-kB Activation in BV2 Microglial Cells

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