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/iota-, partially cyclized mu/nu-, and lambda-carrageenans isolated from the red seaweed Gigartina skottsbergii and their cyclized derivatives was analyzed. lambda-Carrageenans and the partially cyclized mu/nu-carrageenan were the most potent inhibitors of herpes viruses (including acyclovir-resistant variants and clinical isolates), with IC50 values lower than I mu g ml(-1) against both serotypes and selectivity indices higher than 10(3). kappa/iota-Carrageenans were slightly less effective than the other two types with IC50 values in the range 1.6-4.1 mu g 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/nu-type 1C(3) shows the best relationship between antiviral efficacy and lack of anticoagulant action, resulting a Very promising compound. (C) 1997 Elsevier Science B.V.