Antiviral agents. Chemical modifications of a disulfide antibiotic, acetylaranotin

Article abstract of DOI:10.1021/jm00254a010

The reactivity of the cyclic disulfide linkage in acetylaranotin was investigated. Novel insertion reactions with elemental sulfur and hydrogen cyanide gave a tetrasulfide and a dithiocarbamate. Cleavages with methanethiol and dimethyl disulfide gave a dithiol and a bis(methyl disulfide). In mice, the tetrasulfide and a trisulfide gave protection equivalent to that of acetylaranotin against a lethal respiratory virus, Coxsackie A 21. Carbethoxy derivatives were less active. Marginal activities of a trithiocarbonate and a monosulfide give the first indication that an S S linkage may not be an absolute requirement for antiviral activity in this family of compounds. In an enzyme inhibition assay against an RNA polymerase system from Coxsackie A 21 virus, several compounds were more than 1000 times more inhibitory toward the viral polymerase than they were toward the RNA polymerase of the uninfected host cells. An improved color test for detection of thiols is described.