Antiherpetic and anticoagulant properties of carrageenans from the red seaweed Gigartina skottsbergii and their cyclized derivatives: correlation between structure and biological activity.
The antiviral activity against herpes simplex virus types 1 and 2 of kappa/l-, partially cyclized mu/v-, and lambda-carrageenans isolated from the red seaweed Gigartina skottsbergii and their cyclized derivatives was analyzed. lambda-Carrageenans and the partially cyclized mu/v-carrageenan were the most potent inhibitors of herpes viruses (including acyclovir-resistant variants and clinical isolates), with IC50 values lower than 1 microgram ml-1 against both serotypes and selectivity indices higher than 10(3). kappa/l-Carrageenans were slightly less effective than the other two types with IC50 values in the range 1.6-4.1 micrograms ml-1. Antiherpetic activity was directly correlated to the amount of alpha-D-galactose 2,6-disulfate residues in the natural carrageenans. The cyclization of the alpha-D-galactose 6-sulfate and 2,6-disulfate units into 3,6-anhydro-alpha-D-galactose and 3,6-anhydro-alpha-D-galactose 2-sulfate residues in these polysaccharides, in general, lowers the antiherpetic activity of the derivatives with respect to the natural carrageenans. Some carrageenans showed a very reduced anticoagulant activity only at concentrations that were considerably higher than the IC50, whereas others were totally devoid of anticoagulant properties. Among natural carrageenans, the mu/v-type IC3 shows the best relationship between antiviral efficacy and lack of anticoagulant action, resulting a very promising compound.
Carlucci
M J
MJ
Departamento de Quimica Biológica, CIHIDECAR-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Pujol
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Ciancia
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Noseda
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Matulewicz
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Damonte
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Cerezo
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D000818:Animals; D000925:Anticoagulants / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D002351:Carrageenan / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000302:isolation & purification; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D015394:Molecular Structure; D008970:Molecular Weight; D012624:Seaweed / Q000737:chemistry; D013329:Structure-Activity Relationship; D013918:Thrombin Time; D014709:Vero Cells
D000925:Anticoagulants; D000998:Antiviral Agents; D046911:Macromolecular Substances; D002351:Carrageenan