Reversible inhibition of the reproducton of DNA viruses by glycosides of 2-phenethyl alcohol and related compounds

Abstract

Phenylethyl alcohol and related compounds are able to inhibit the reproduction of DNA viruses but not the reproduction of RNA viruses in tissue culture. Since phenylethyl alcohol and particularly the analogous compounds P-nitrophenylethyl alcohol and phenylpropyl alcohol have a high toxicity for tissue cultures, an attempt was made to attain a similar inhibition of virus synthesis but a lower level of toxicity through administration of the glycosides of these aromatic alcohols. For this purpose the following glycosides were synthesized: Phenylethyl galactoside; P-Nitrophenylethyl galactoside; Phenylpropyl galactoside; Phenylethyl glucoside; Phenylethyl glucuronide. The corresponding glycosidases, β-galactosidase, β-glucosidase and β-glucuronidase could be detected and their activity measured in monkey kidney and HeLa cell tissue cultures. In addition, it was possible to localize the enzyme activities histochemically by using glycosides of 4-methylumbelliferone. The effect of the synthesized glycosides on the reproduction of DNA viruses (Vaccinia virus, Herpes simplex virus, SV-40) and RNA viruses (Poliovirus type 1) was investigated. The efficacy of the glycosides is dependent upon the type of glycone. The galactosides have the greatest inhibitory effect while the glucuronide of phenylethyl alcohol shows no effect at all on the replication of Vaccinia virus. The glycosides investigated possess a lower toxicity than the free alcohol; HeLa cells are more sensitive towards the compounds than monkey kidney cells. The use of virus inhibiting compounds in the form of glycosides therefore makes it possible for the active substances to be brought into the cell in a non-toxic form and to be transformed into the active compound by the cell enzymes.