Can chelation be important in the antiviral activity of isatin β-thiosemicarbazones?

Abstract

The stability constants of 5-sulfonatoisatin β-thiosemicarbazone (β-thiosemicarbazonoisatin-5- sulfonate) [sibt,(3)] with Zn2+ and Fe2+ have been determined from slow pH titrations (I 0.15M KNO3, 37�). At pH 7.4, the conditional stability constants for the sibt complexes are logK1' 4.5 (Zn2+), 3.1 (Fe2+) and log β2' 8.9 (Zn2+), 6.5 (Fe2+). The mixed ligand complexes Zn(sibt)L (L = histidine or glycine) have conditional stability constants log β1110' 8.8 and 7.0, respectively, at pH 7.4. Copper(I) complexes of sibt and bishistidinato-copper(II) coexist in mixtures of Cu2+, sibt and histidine. [In solutions of copper ions, sibt (complexes Cu+) and histidine (chelates Cu2+), the response of the Orion cupric-ion-selective electrode is not stoichiometric.] Also studied was 1-methyl-5-sulfonatoisatin β-thiosemicarbazone [msibt,(4)] which behaves like sibt. 5-Sulfonatoisatin β-semicarbazone and p-sulfonatobenzaldehyde thiosemicarbazone (p-thiosemicarbazonomethyl- benzenesulfonate) are weak ligands. Comparison of the stability constants with those of complexes of biologically relevant chelating agents showed that isatin β-thiosemicarbazones are not expected to form stable complexes with zinc and iron in vivo. Bidentate thiosemicarbazones, such as benzaldehyde thiosemicarbazones, form even weaker complexes. Both classes of thiosernicarbazones have a similar activity against vaccinia virus; this activity seems not to depend on metal ion chelation.