Effects of Some Antiviral Isatinisothiosemicarbazones on Cellular and Viral Ribonucleic Acid Synthesis in Mengovirus-Infected FL Cells

Abstract

Three antiviral isatinisothiosemicarbazones strongly inhibited the incorporation of [8H ]uridine into the ribonucleic acid (RNA) of FL cells as a consequence of the inhibition of uridine transport. After prelabeling of cells at a low temperature (1 h at 16 C) with uptake of [3H]uridine into the acid-soluble nucleotide pool, the later addition of the test compounds revealed only a sniall or negligible influence on host-directed RNA synthesis. The pulse-labeled soluble nucleotide pool of FL cells was sufficient to give a gradual increase in incorporation into RNA over a period of 7 h. With the same method of prelabeling at the beginning of the experiment, it was also possible to detect virus-induced RNA synthesis in the presence of actinomycin D. In this way the specific inhibitory action of the three isatinisothiosemicarbazones on viral RNA synthesis could be demonstrated.

Effect of Solvent Polarizability on the Keto/Enol Equilibrium of Selected Bioactive Molecules from the 1,3,4-Thiadiazole Group with a 2,4-Hydroxyphenyl Function

“…These compounds are used as colorants, and metal complexing agents. 1,2 Additionally, 1,3,4thiadiazoles exhibit antitumor, 3 antifungal, 4 antibacterial, 4 antiinflammatory, 5 anticonvulsant, 6 antiviral, 7 antituberculosis, 8 antihypertensive, 9 and antidepressant 10 activity. Three promising 1,3,4-thiadiazole analogues with proven antitumor activity were chosen for investigations of the mechanism of molecular interactions; these were 4-(5-(methylamino)-1,3,4-thiadiazol-2-yl)benzene-1,3-diol (MDFT), 4-(5-(phenylamino)-1,3,4-thiadiazol-2-yl)benzene-1,3-diol (PhATB), and 4-(5-(4-chlorophenylamino)-1,3,4thiadiazol-2-yl)benzene-1,3-diol (4-CIPhATB) (Scheme 1A and B, R 1 , R 2 and R 3 , respectively).…”

The Thiosemicarbazones

“…Isatin-p-Isothiosemicarbazones TONEW and TONEW (1974) found that tritiated uridine incorporation into the RNA of normal human amnion (FL) cells was reduced by 80% within 6 h after addition of anyone of three isothiosemicarbazones ( Fig. 13) at concentrations that would almost completely block Mengo virus synthesis in these cells.…”

“…The latter was measured by the loss of ability of virus-specific antibody to neutralize cell-adsorbed virus. Extending these studies to include N 1 -methyl-isatin-S-ethylisothiosemicarbazone and N1-ethylisatin-S-n-butylisothiosemicarbazone TONEW and TONEW (1974) found that these compounds inhibited uridine transport in uninfected FL cells (Sect. E.V).…”