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 microg/ml (2,5-DHBQOP). The CC50 values of the polymers varied among 32.0 (TMHYDROP) and >512 microg/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 microg/ml, respectively, and SI: > or = 400, > or = 80 and > or = 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.
Klöcking
R
R
Institute for Antiviral Chemotherapy, Friedrich-Schiller-University Jena, Jena, Germany. rkloeck@zmkh.ef.uni-jena.de
Helbig
B
B
Schötz
G
G
Schacke
M
M
Wutzler
P
P
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D006812:Humic Substances / Q000737:chemistry / Q000494:pharmacology*; D007928:Lethal Dose 50; D008970:Molecular Weight; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D014709:Vero Cells / Q000187:drug effects / Q000821:virology; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D006812:Humic Substances; D010636:Phenols; D011108:Polymers