Polyanion Inhibitors of Human Immunodeficiency Virus and Other Viruses. 5. Telomerized Anionic Surfactants Derived from Amino Acids

• Published in: Journal of medicinal chemistry Vol. 40; no. 3; pp. 342 - 349
• Main Authors: Leydet, Alain, Barragan, Véronique, Boyer, Bernard, Montéro, Jean Louis, Roque, Jean Pierre, Witvrouw, Myriam, Este, José, Snoeck, Robert, Andrei, Graciela, De Clercq, Erick
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 31-01-1997
• Subjects: Amino Acids - chemistry; Animals; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Biological and medical sciences; Cell Line; Cytomegalovirus - drug effects; DNA Viruses - drug effects; DNA Viruses - metabolism; HIV-1 - drug effects; HIV-2 - drug effects; human immunodeficiency virus; Humans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medical sciences; Microbial Sensitivity Tests; Molecular Conformation; Molecular Structure; Pharmacology. Drug treatments; Polymers - chemical synthesis; Polymers - chemistry; Polymers - pharmacology; RNA Viruses - drug effects; RNA Viruses - metabolism; Simplexvirus - drug effects; Surface-Active Agents - chemical synthesis; Surface-Active Agents - chemistry; Surface-Active Agents - pharmacology; Cytomegalovirus; Polyanion; Herpesviridae; Alphaherpesvirinae; Retroviridae; Betaherpesvirinae; In vitro; Acrylamide derivative polymer; Virus; Anionic surfactant; α-Aminoacid; Structure activity relation; Telomerization; Carboxylate; Lentivirinae; Antiviral; Herpesvirus hominis; Human immunodeficiency virus; Chemical synthesis
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm960493b

ω-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 μg/mL, or even 0.1 μg/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 μg/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 μg/mL.