Betulinic Acid Derivatives: A New Class of Human Immunodeficiency Virus Type 1 Specific Inhibitors with a New Mode of Action
Autor: | A. Bousseau, Y. Lelievre, Y. Ribeill, N Dereu, J.-C. Gueguen, Y. Henin, J.-B. Le Pecq, M. Evers, F. Soler, E. De Clercq, D. Reisdorf, I. Morize, J F Mayaux, Rudi Pauwels, C Poujade, C. James |
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Rok vydání: | 1996 |
Předmět: |
Models
Molecular Stereochemistry medicine.medical_treatment Carboxylic acid Antiviral Agents Virus Structure-Activity Relationship chemistry.chemical_compound Betulinic acid Drug Discovery Tumor Cells Cultured medicine Humans Structure–activity relationship Enzyme Inhibitors Betulinic Acid Mode of action chemistry.chemical_classification Protease Molecular Structure Chemistry virus diseases Triterpenes In vitro Biochemistry HIV-2 HIV-1 Reverse Transcriptase Inhibitors Molecular Medicine Primer (molecular biology) Pentacyclic Triterpenes |
Zdroj: | Journal of Medicinal Chemistry. 39:1056-1068 |
ISSN: | 1520-4804 0022-2623 |
DOI: | 10.1021/jm950670t |
Popis: | A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and evaluated for activity in CEM 4 and MT-4 cell cultures against human immunodeficiency virus type 1 (HIV-1) strain IIIB/LAI. The potent HIV inhibitors which emerged, compounds 5a, 16a, and 17b, were all derivatives of betulinic acid (3beta-hydroxylup-20(29)-en-28-oic acid). No activity was found against HIV-2 strain ROD. Compound 5a showed no inhibition of HIV-1 reverse transcriptase activity with poly(C).oligo(dG) as template/primer, nor did it inhibit HIV-1 protease. Additional mechanistic studies revealed that this class of compounds interfere with HIV-1 entry in the cells at a postbinding step. |
Databáze: | OpenAIRE |
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