Inhibition of Moloney Leukaemia Virus Production by N-methylisatin-beta-4':4'-diethylthiosemicarbazone

Abstract

SUMMARYN-methylisatin-fl-4':4'-diethylthiosemicarbazone (M-IBDET) inhibited the production of Moloney leukaemia virus (MLV). Virus inhibition was related to drug concentrations and time of treatment. The effective antiviral drug concentrations ranged between 3"4/ZM and 34/ZM. Virus reverse transcriptase activity even at concentrations of 34 #M-M-IBDET was not inhibited. At virus inhibitory concentrations the drug reduced RNA synthesis only very slightly and did not affect protein synthesis at all, although growth and DNA synthesis of host cells were suppressed. The inhibition of cellular DNA synthesis was reversible. Comparison of M-IBDET with actinomycin D, cycloheximide and c~-amanitin in terms of their inhibitory effect on the release of MLV into the culture medium showed that M-IBDET was comparable to the other antimetabolites. The inhibition of MLV production by M-IBDET was confirmed by various parameters of virus assay. It was concluded from the experimental evidence that M-IBDET specifically inhibits MLV production.

Inhibition of Feline Immunodeficiency Virus Production and HIV Tat Activity by Thiosemicarbazone Derivatives

“…Various derivatives of TSC act as inhibitors of DNA and RNA viruses (O'Sullivan et al, 1963;Pearson and Zimmerman, 1969). We were the first to show that M-IBDET inhibits the production of M-MuLV Sherman et al, 1980), a member of the retrovirus family. It was shown that M-IBDET specifically inhibits M-MuLV structural protein synthesis by blocking the translation process of M-MuLV mRNA (Ronen and Teitz, 1984;Ronen et al, 1985Ronen et al, , 1987 In an attempt to understand the inhibition of FIV by the TSCD, we examined the effect of A-IBDAT on the synthesis of the FIV gag gene encoding p24 protein.…”

“…The exogenous reaction was performed as described previously (Sherman et al, 1980) in the presence of 10 mMMg++ in the reaction mixture.…”

“…Our previous studies demonstrated that TSCD inhibit murine retrovirus structural protein synthesis without affecting cellular protein synthesis or cell growth. TSCD varied in their effect on cellular DNA synthesis (Sherman et al, 1980). We have therefore synthesized new TSCD which have antiretroviral activity with the object of choosing those TSCD that have minimal effects on cell growth and the highest therapeutic index (TI) (Teitz et al, 1994).…”

Quantum Chemical Calculations for some Isatin Thiosemicarbazones

“…N-methylisatin--4', 4' -diethylthiosemicarbazone were also reported to have activity against the viruses such as cytomegalo and moloney leukemia viruses (Sherman et al, 1980;Ronen et al, 1987). With the help of combinatorial method, the cytotoxicity and antiviral activities of isaitin--thiosemicarbazones against the vaccine virus and cowpox virus-infected human cells were evaluated (Pirrung et al, 2005).…”

Selective repression of v-abl-encoded protein by N-methylisatin-beta-4',4'-diethylthiosemicarbazone and N-allylisatin-beta-4',4'-diallylthiosemicarbazone

“…N-Methylisatin-P-4',4'-diethylthiosemicarbazone (M-IBDET) at concentrations between 3.4 and 34 p,M specifically suppressed M-MuLV production in NIH 3T3/M-MuLV cells (14). M-IBDET inhibits viral synthesis by blocking the translation of viral polyprotein precursors, thus suppressing viral structural protein production (9,11).…”