Polyanion inhibitors of human immunodeficiency virus and other viruses. 5. Telomerized anionic surfactants derived from amino acids.
omega-Acryloyl anionic surfactants, whose polar heads are derived from amino acids, have been telomerized to prepare polyanions of a predetermined molecular weight. The main goal of this study was to verify whether the antiviral activity is influenced by the degree of polymerization of the polyanions. The oligomeric polyanions were evaluated for their activity against human immunodeficiency virus (HIV-1 or HIV-2) and various other RNA and DNA viruses. With regard to their anti-HIV activity, a minimum number of anionic groups was necessary to achieve an inhibitory effect. Moreover, to be active the overall conformation of the polyanion must be such that the anionic groups are located on the external site of the molecule. With some of the polyanions, a 50% inhibition concentration (IC50) as low as 1 microgram/ mL, or even 0.1 microgram/mL, was noted against HIV-1 in CEM-4 and MT-4 cells, respectively. The most potent polyanions also proved active against human cytomegalovirus and herpex simplex virus at concentrations of 5-10 and 20-40 micrograms/mL, respectively. No activity was observed against any of the other viruses tested (i.e., vesicular stomatitis, Sindbis, Semliki forest, parainfluenza, Junin, Tacaribe, Coxsackie, polio, reo, and vaccinia). No toxicity for the host cells was observed at concentrations up to 200 micrograms/mL.
Leydet
A
A
Laboratoire de Chimie Organique Physique, Université de Montpellier II, France.
Barragan
V
V
Boyer
B
B
Montéro
J L
JL
Roque
J P
JP
Witvrouw
M
M
Este
J
J
Snoeck
R
R
Andrei
G
G
De Clercq
E
E
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects; D004267:DNA Viruses / Q000187:drug effects / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D015394:Molecular Structure; D000071228:Polyelectrolytes; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012328:RNA Viruses / Q000187:drug effects / Q000378:metabolism; D018139:Simplexvirus / Q000187:drug effects; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000596:Amino Acids; D019380:Anti-HIV Agents; D000998:Antiviral Agents; D000071228:Polyelectrolytes; D011108:Polymers; D013501:Surface-Active Agents