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
Rok vydání: 1996
Předmět:
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