ANTI-HERPES SIMPLEX VIRUS TYPE-1 ACTIVITY OF HUMIC ACID-LIKE POLYMERSAND THEIR O-DIPHENOLIC STARTING COMPOUNDS

Phenolic polymers of the humic acid (HA) type, like other polyanionic substances, are inhibitors of herpes simplex virus type 1 (HSV-1) repl ication. The antiviral potency of the low molecular weight (MW) phenol ic starting compounds has not been investigated systematically up to n ow. To reveal possible relationships between the chemical structure of o-diphenolic starting compounds and the anti-HSV-l activity of HA-lik e polymers, nine polymers were synthesized by oxidation of the corresp onding o-dihydroxybenzene derivatives. They were characterized by MW d istribution, Fourier transform infra-red spectra and functional group analysis. Using an XTT-based tetrazolium reduction assay, both the low MW starting compounds and the synthesized polymers were examined for their antiviral and cytotoxic activities in HSV-l-infected Vero cells. The results demonstrate that most of the starting compounds failed to inhibit herpesvirus replication. The polymeric oxidation products (OF ), however, developed detectable anti-HSV-l activity with IC50 values in the range 2.3 [the OP of 3,4 dihydroxycinnamic acid (caffeic acid); KOP] to 42.1 mu g ml(-1) (3,4-dihydroxytoluene OF). The CC50 of polym ers varied between 40.8 (3,4-dihydroxybenzaldehyde OP) and >128 mu g m l(-1) (most polymers). Functional group analysis revealed that the pre sence of carboxylic groups in the starting compounds enhanced the anti viral activity and reduced the cytotoxicity of polymers. The introduct ion of a C=C double bond into the side chain [i.e. caffeic acid; 3-0-( 3,4-dihydroxycinnamoyl)-D-chinic acid (chlorogenic acid; CH)I yielded the most effective polymers (KOP, CHOP). These may be considered as le ader substances for HSV-1 inhibitors of the HA type.