Anti-HSV-1 Activity of Synthetic Humic Acid-Like Polymers Derived from p -Diphenolic Starting Compounds

A panel of ten humic-acid-like polymers was synthesized by oxidation of p -diphenolic compounds and characterized by relative molecular weights, FT-IR spectra and functional group analysis. Using the XTT-based tetrazolium reduction assay EZ4U, both the low-molecular starting compounds and the synthesized polymers were examined for antiviral and cytotoxic activities in HSV-1-infected Vero cells. With the exception of hydroquinone, 2,5-dihydroxytoluene and 2,5-dihydroxybenzoquinone, the starting compounds failed to inhibit herpesvirus replication. The polymeric oxidation products, however, developed anti-HSV-1 activity with EC₅₀ values in the range of 0.65 (2,5-DHPOP) and 322 μg/ml (2,5-DHBQOP). The CC₅₀ values of the polymers varied among 32.0 (TMHYDROP) and >512 μg/ml (2,5-DHBQOP, HYDSULFOP). The most effective polymers were found to be 2,5-DHPOP, 2,5-DHTOP and GENOP (EC₅₀: 0.65, 1.6 and 2.2 μg/ml, respectively, and SI: ≥400, ≥80 and ≥58, respectively). Functional group analysis revealed that increasing numbers of carboxyl groups together with a high content of hydroxyl groups tend to enhance the antiviral activity of polymers derived from p -diphenolic compounds.