Polyanion inhibitors of human immunodeficiency virus and other viruses. 6. Micelle-like anti-HIV polyanionic compounds based on a carbohydrate core.
A new class of polyanionic compounds, inhibitors of human immunodeficiency virus, was obtained from radical addition of mercapto acid or mercapto ester on a perallylated carbohydrate under UV irradiation with a catalytic amount of AIBN. Unlike the polyanions that we have previously prepared by polymerization reactions, the compounds are structurally well defined. Polyanions bearing 16 carboxylate groups showed a 50% inhibitory concentration (IC50) of 0.1-4.1 micrograms/mL against HIV-1 in MT-4 cells while not being toxic to the host cells at concentrations up to 125 micrograms/mL. The most potent polyanions also proved active against human cytomegalovirus at concentrations of 1-14 micrograms/mL. No activity was observed against any of the other viruses tested (i.e., herpes simplex virus, vesicular stomatitis virus, Sindbis, Semliki forest, parainfluenza-3, Junin, Tacaribe, Coxsackie B4, polio-1, reo-1, or vaccinia virus).
Leydet
A
A
Laboratoire de Chimie Organique Physique, Université Montpellier II, France.
Jeantet-Segonds
C
C
Bouchitté
C
C
Moullet
C
C
Boyer
B
B
Roque
J P
JP
Witvrouw
M
M
Este
J
J
Snoeck
R
R
Andrei
G
G
De Clercq
E
E
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002241:Carbohydrates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008823:Micelles; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009570:Nitriles / Q000494:pharmacology; D000071228:Polyelectrolytes; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014466:Ultraviolet Rays
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D002241:Carbohydrates; D008823:Micelles; D009570:Nitriles; D000071228:Polyelectrolytes; D011108:Polymers; C004526:azobis(isobutyronitrile)