Inhibition of human immunodeficiency virus by N-methylisatin-beta 4':4'-diethylthiosemicarbazone and N-allylisatin-beta-4':4'-diallythiosemicarbazone.
N-methylisatin-beta 4':4'-diethylthiosemicarbazone(M-IBDET) and N-allylisatin-beta-4':4'-diallylthiosemicarbazone(A-IBDAT ) inhibit the production of Human Immunodeficiency virus (HIV). Virus inhibition was related to the thiosemicarbazone derivative (TSCD) concentrations and time of treatment. Inhibition of HIV production was confirmed by various parameters of virus assay employing reverse transcriptase activity, plaque forming units (PFU) and levels of viral structural proteins. Effective antiviral TSCD concentrations ranged from 0.17 microM to 2.04 microM for M-IBDET, and from 1.45 microM to 17.4 microM for A-IBDAT. Treatment of the chronic HIV-infected cells for 48 h with 0.34 microM M-IBDET or 2.9 microM A-IBDAT caused about 50% inhibition in as virus yield ED50 as assayed by the PFU method. Almost 2 logs of virus infectivity (PFU) was suppressed after 48 h of treatment with 17.4 microM A-IBDAT. Therapeutic index values of 20 and 30 were found for M-IBDET and A-IBDAT, respectively. A significant selective inhibition of HIV structural protein synthesis was shown by both M-IBDET and A-IBDAT.
Teitz
Y
Y
Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Israel.
Ronen
D
D
Vansover
A
A
Stematsky
T
T
Riggs
J L
JL
D000998:Antiviral Agents / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects*; D006801:Humans; D007510:Isatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008720:Methisazone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000821:virology; D013882:Thiosemicarbazones / Q000494:pharmacology*; D015678:Viral Structural Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D013882:Thiosemicarbazones; D015678:Viral Structural Proteins; C085307:N-allylisatin-beta-4',4'-diallylthiosemicarbazone; C022832:N-methylisatin beta-4',4'-diethylthiosemicarbazone; D007510:Isatin; D008720:Methisazone