New anti-HIV derivatives: synthesis and antiviral evaluation.
A small focused library of 18 compounds incorporating the motif 1,3-(N,N'-dibenzyl)diamino-2-propanol has been synthesized, using adapted synthetic methodologies. These series of compounds were evaluated for their in vitro anti-HIV activity on infected MT4 cells (syncytium formation observation). Some of the new synthesized compounds show potent anti-HIV activities. EC50 values for compounds (31, 40, 34, 37 and 46) range from 0.1 to 1 microM. In order to determine at which level these new derivatives interfere with the HIV replicative cycle, inhibition assays on recombinant HIV protease and HIV integrase have been performed. None of the compounds were found active on these two enzymatic targets. Experiments are in progress in order to identify their biological target within the HIV replicative cycle.
De Michelis
C
C
Laboratoire de Chimie Biomoléculaire, Faculté des Sciences de Luminy, Université de la Mediterranée, Marseille, France.
Rocheblave
L
L
Priem
G
G
Chermann
J C
JC
Kraus
J L
JL
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D015726:Giant Cells; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors