TY - JOUR
T1 - New synthetic glutathione derivatives with increased antiviral activities
AU - Palamara, Anna Teresa
AU - Brandi, Giorgio
AU - Rossi, Luigia
AU - Millo, Enrico
AU - Benatti, Umberto
AU - Nencioni, Lucia
AU - Iuvara, Alessandra
AU - Garaci, Enrico
AU - Magnani, Mauro
PY - 2004/3
Y1 - 2004/3
N2 - A series of glutathione (GSH) derivatives with aliphatic chains of different lengths, coupled by peptides bound to the α-NH2 group of Glu, were synthesized. When added to several cell lines, the C6 (n-hexanoyl), C8 (n-octanoyl) and C12 (n-dodecanoyl) derivatives were toxic while the C2 (n-ethanoyl) and C4 (n-butanoyl) derivatives were not. Preliminary experiments were performed to investigate the potential antiviral activity of the C2 and C4 derivatives compared to GSH. The C4 derivative was the most potent and fully characterized. GSH-C4 is a poor substrate of GSH metabolizing enzymes; once oxidized by disulphide-bound formation, C4 is slowly reduced by GSH-reductase. GSH-C4 completely abrogated Sendai virus replication at 7.5 mM with an EC50 of 3.6 mM, compared to 7.5 mM for GSH. GSH-C4 completely inhibited herpes simplex virus (HSV-1) virus production in Vero cells at 10 mM, while the same dose of GSH caused only a 2.5 log10 reduction. Furthermore, the GSH-C4 treatment (7.5 mM) was able to markedly reduce the cytopathic effect of HSV-1 in Vero cells. Thus, GSH derivatives with increased hydrophobic properties are more effective antiviral agents against Sendai and HSV-1 viruses than GSH, suggesting their usefulness in antiviral therapy.
AB - A series of glutathione (GSH) derivatives with aliphatic chains of different lengths, coupled by peptides bound to the α-NH2 group of Glu, were synthesized. When added to several cell lines, the C6 (n-hexanoyl), C8 (n-octanoyl) and C12 (n-dodecanoyl) derivatives were toxic while the C2 (n-ethanoyl) and C4 (n-butanoyl) derivatives were not. Preliminary experiments were performed to investigate the potential antiviral activity of the C2 and C4 derivatives compared to GSH. The C4 derivative was the most potent and fully characterized. GSH-C4 is a poor substrate of GSH metabolizing enzymes; once oxidized by disulphide-bound formation, C4 is slowly reduced by GSH-reductase. GSH-C4 completely abrogated Sendai virus replication at 7.5 mM with an EC50 of 3.6 mM, compared to 7.5 mM for GSH. GSH-C4 completely inhibited herpes simplex virus (HSV-1) virus production in Vero cells at 10 mM, while the same dose of GSH caused only a 2.5 log10 reduction. Furthermore, the GSH-C4 treatment (7.5 mM) was able to markedly reduce the cytopathic effect of HSV-1 in Vero cells. Thus, GSH derivatives with increased hydrophobic properties are more effective antiviral agents against Sendai and HSV-1 viruses than GSH, suggesting their usefulness in antiviral therapy.
KW - Antiviral efficacy
KW - Glutathione derivatives
KW - Herpes simplex-1
KW - Sendai virus
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M3 - Article
C2 - 15185726
AN - SCOPUS:2342457025
VL - 15
SP - 83
EP - 91
JO - Antiviral Chemistry and Chemotherapy
JF - Antiviral Chemistry and Chemotherapy
SN - 0956-3202
IS - 2
ER -