Antiviral activity thiosemicarbazones

Virus replication comprises numerous biochemieal transformations that might provide suitable targets for antiviral therapy. The antiviral effect of thiosemicarbazones was first demonstrated by Hamre et al. [53, 54], who showed that p-aminobenzaldehyde-3-thiosemicarbazone and several of its derivatives were active against vaccinia virus in mice. These studies were extended to include thiosemicarbazones of isatin, benzene, thiophene, pyridine, and quinoline derivatives, which also showed activity against vaccinia-induced encephalitis. The nature of the aldehyde/ketone moiety was not as significant as the presence of the thiosemicarbazide side chain the latter was deemed essential for antiviral activity. 

Eucka-Sobstel, B.. Zeic. A., Borysiewicz, J., and I )tec. Z., In vitro antiviral activity of Mannich ba.ses derived from 5-bromoisatin and its p-thiosemicarbazone, Acta Pharm. Jiigosi, 4,95. 1974 Chem. Ahstr, 82,25652, 1975. 

The thiosemicarbazone of 7-azaisatin lacked antiviral activity isatin and pyridinecarboxaldehyde derivatives are active. ... 

Replacement of the sulfur atom in the thiosemicarbazone moiety by an oxygen atom leads to a loss of antiviral activity. Methisazone has no significant effect on vaccinia virus DNA synthesis (14) but seems to inhibit late protein synthesis by a mechanism that remains to be elucidated. 

Some aromatic thiosemicarbazones are active against smallpox virus, while phosphonoformic acid (PFA) and phosphonoacetic acid (PAA) are active against herpes viruses. Consequently, some acylphosphonate thiosemicarbazones, (47), in which the two types of structural moieties appear together, were synthesized and tested for antiviral activity. However, no inhibitory activity was observed against herpes and/or pox viruses . 

The a-(AO-heterocycIic carboxaldehyde thiosemicarbazones constitute a class of agents which possess both antineoplastic and antiviral activity [1], The first agent of this series to be examined for biological activity, 2-formylpyridine thio-... 

Thus, the antiviral activity of the thiosemicarbazones has been correlated, in one study, with their ability to inhibit ribonucleotide reductase [8]. Methisazone inhibits the RNA-dependent DNA polymerase of Rous sarcoma virus (RSV) and inactivates its ability to transform chick-embryo cells [9], as well as inactivating herpes simplex [10] and some RNA viruses [11]. The activity against RSV is Cu-dependent [9], the Cu complex also being capable of inhibition of the polymerase [12]. Since these enzymes are zinc-dependent, interference with the role of zinc is possible. The inhibition of influenza virus-associated RNA transcriptase by... 

Chelating agents may manifest their antiviral activity by metal sequestration and, as with bacteria and parasites, the natural differences between the host and invading cells may be exploited. Chelating agents with antiviral activity include the thiosemicarbazones, 1,10-phenanthrolines and phosphonoacetates. The latter compounds may act by zinc chelation. Metal complexes with antiviral action are platinum and palladium amines, as well as the antibacterial silver and mercury species. 

Pharmacologically Active Compounds.— Benzo[6]thiophen-2- and -3-carbox-aldehyde thiosemicarbazones have been prepared and screened for antiviral activity. 3-Benzo[fe]thiophenoxyaminopropanols and the complex benzo[6]-... 

Among biologically active compounds - derivatives of isatin - there is methisazone (1-methylisatin 3-thiosemicarbazone), which has been used as a prophylactic agent against the smallpox virus [139-141], Methods for the synthesis of compounds with the general formula 146 have been developed in the search for new antiviral and antimicrobial agents [142] ... 

Isatin-j8-thiosemicarbazone was originally found to be a potent antivaccinia viral agent in mice and the activity of this compound was attributed to complex formation [545]. Subsequently, a derivative, jV-methylisatin-3-thiosemicarbazone (M-IBT), proved to be a very effective antiviral agent in humans for the prevention of morbidity and mortality due to smallpox epide-... 

Anticancer examples, Thiosemicarbazones have been mentioned above in connexion with their antiviral and antitubercular properties. They also have anticancer activity, as already mentioned for 5-hydroxypicolinic aldehyde thiosemicarbazone (4.18) in Section 4.0. Such substances powerfully inhibit ribonucleoside diphosphate reductase, the enzyme which converts ribo- to deoxyribo- nucleotides, leading to inhibition of DNA synthesis. Interaction with the enzymatically-required iron by these drugs in thought to lie at the root of their action (Agrawal, et al,y 1972). 

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