Dereu N, Evers M, Soler F, Poujade C, Henin Y, Mayaux JF; International Conference on AIDS.

Int Conf AIDS. 1993 Jun 6-11; 9: 229 (abstract no. PO-A25-0568).

Rhone-Poulenc Rorer Central Research--Vitry sur Seine, France.

OBJECTIVE: A series of original triterpene derivatives have been synthesized and screened in a HIV1 infected cell assay. METHODS: The anti-HIV1 activity (CPE) was investigated in CEM and MT4 cells using a tetrazolium-based viability assay. RESULTS: A new triterpene derivative RP 70034 was found to display a potent inhibition of HIV1 replication (EC50 = 300 nM/CEM). Analogous derivatives of other triterpenes were found to be inactive. The influence of backbone modifications in ring A and E was investigated. In particular, the 3-beta hydroxy moiety was found essential for optimal activity. Potency was also found to be strongly related to the nature and the length of the lateral chain. The introduction of an amide function within the chain modulated activity and, in the case of RPR 100399, increased activity to EC50 = 150 nM/CEM. Further structural modifications on the terminal amino acid of the lateral chain led to RPR 103611, a derivative with improved efficacy (EC50 = 50 nM/CEM and 40 nM/MT4). These triterpene derivatives proved inactive on HIV1 protease and reverse transcriptase, as well as on gp120: CD4 binding, therefore suggesting an original mode of action.

Publication Types:

• Meeting Abstracts

Keywords:

• Anti-Anxiety Agents
• HIV Envelope Protein gp120
• HIV Protease
• HIV Protease Inhibitors
• HIV-1
• RNA-Directed DNA Polymerase
• RPR 103611
• Structure-Activity Relationship
• Triterpenes
• immunology
• reverse transcriptase, Human immunodeficiency virus 1

Other ID:

• 93334033

UI: 102203407

From Meeting Abstracts