The Effect of Isatin beta Thiosemicarbazone (IBT)-related Compounds on IBT-resistant and on IBT-dependent Mutants of Vaccinia Virus

Abstract

SUMMARYIBT-related compounds were examined for their ability to inhibit wild-type and IBT-resistant mutants of vaccinia virus and for their capability to support the growth of an IBT-dependent mutant. Among thirteen compounds tested, six did not affect any one of the three virus strains and five behaved similarly to IBT, but two inhibited the growth of all three viruses and therefore differed from IBT. It was found that the Iast two compounds also differed from IBT in that they interfered with synthesis of the virus DNA. This difference is surprising in view of a substantial similarity in chemical structure.

The Thiosemicarbazones

“…15) which was reported to have antipox activity in mice, was 4-methyl-5-formylthiazole-TSC (CAMPAIGNE et al 1959). This observation has been confirmed in tissue culture using 5-formylthiazole-TSC (KATZ et al 1974). Little information is available on structure-activity relationships aside from the finding that placing the TSC side chain in the 4 position (a to the ring nitrogen atom; see Sects.…”

“…No additive effect of the two compounds was observed in the animal tests. The thiochromanone-TSC activity in tissue culture has been confirmed (KATZ et al 1974(KATZ et al , 1975. A single report (Buu-HOI et al 1968) exists indicating that 3,9-diethyl-6-formylcarbazole-TSC (Fig.…”

“…8, Rl = H or CH 3 , R2 = H, R3 = H 2 , X = S). KATZ et al (1974) found that 5-hydroxy-2-formylpyridine-TSC (Fig.4) and I-formylisoquinoline-TSC (Fig. 6) would prevent vaccinia plaque formation in tissue culture.…”

“…Parenthetically, one notes that the minimum requirement for antitumor activity of pyridine-and isoquinoline-TSCs is that the TSC side chain must be attached a to an unencumbered ring nitrogen atom (AGRAWAL and SARTORELLI 1978). Although the thiophene-TSCs have received little attention (KATZ et al 1974), 5-cyanothiophene-2-formylthiosemicarbazone ( Fig. 7) has been reported to be superior to I-methylisatin-p-thiosemicarbazone in its in vivo antivaccinia activity in several animal species (Sects.…”

Isolation and Characterization of a γ-Thiochromanone-4-Thiosemicarbazone-Resistant Mutant of Vaccinia Virus

“…Tsunoda et al (17) reported that y-thiochromanone-4-thiosemicarbazone (TCT) is also an efficient inhibitor of poxvirus in chicken cells in vitro and in the mouse. Thiosemicarbazone-related compounds, which inhibit the growth of poxviruses, are able to do so either by inhibiting deoxyribonucleic acid (DNA) synthesis or by blocking a maturational event (5).…”