Zinc(II) complexes derived from pyridine-2-carbaldehyde thiosemicarbazone and (1E)-1-pyridin-2-ylethan-1-one thiosemicarbazone. Synthesis, crystal structures and antiproliferative activity of zinc(II) complexes.

The complexes [ZnCl(2)(HFoTsc)xH(2)O], [Zn(FoTsc)(2)], [ZnCl(2)(HAcTsc)xH(2)O] and [Zn(AcTsc)(2)], where HFoTsc and HAcTsc is pyridine-2-carbaldehyde thiosemicarbazone and (1E)-1-pyridin-2-ylethan-1-one thiosemicarbazone respectively, have been prepared and structurally characterized by means vibrational, and NMR ((1)H and (13)C) spectroscopy. The crystal structures of the complexes [ZnCl(2)(HFoTsc)xH(2)O], [Zn(AcTsc)(2)] and [ZnCl(2)(HAcTsc)xH(2)O] have been determined by X-ray crystallography. The metal co-ordination geometry of [ZnCl(2)(HFoTsc)xH(2)O] and [ZnCl(2)(HAcTsc)xH(2)O] is described as distorted square pyramidal and the two complexes are self-assembled via pi-->pi stacking interactions and intermolecular hydrogen bonds. In these two cases molecular recognition of the hydrogen bonds leads to aggregation and a supramolecular assembly of infinite two-dimensional network. The metal co-ordination geometry of [Zn(AcTsc)(2)] is described as distorted octahedral configuration in a trans-N(2)-cis-N(1)-cis-S configuration. HFoTsc and HAcTsc and the zinc complexes have been evaluated for antiproliferative activity in vitro against the cells of two human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line) and a mouse fibroblast L-929 cell line. The cytotoxic activity shown by these compounds indicates that coupling of HFoTsc and HAcTsc to Zn(II) metal center result in metallic complexes with important biological properties since they display IC(50) values in a microM range similar to or better than that of the antitumor drug cis-platin and are considered as agents with potential antitumor activity candidates for further stages of screening in vitro and/or in vivo.

Toxic effects of bis(thiosemicarbazone) compounds and its palladium(II) complexes on herpes simplex virus growth.

Here, we present data on the activity of benzyl bis(thiosemicarbazone); 3,5-diacyl-1,2,4-triazole bis(4-methylthiosemicarbazone) and their Pd(II) complexes against the replication of wild type and of acyclovir (ACV)-resistant, herpes simplex virus type 1 (HSV 1) and type 2 (HSV 2) strains. The data were compared to those under the action of acyclovir. The testing of cytotoxic activity suggests that these compounds may be endowed with important antiviral properties. It is interesting to note that the Pd(II)-benzyl bis(thiosemicarbazone) complex, 2, exhibits a significant activity against acyclovir-resistant viruses R-100 (HSV 1) and PU (HSV 2) with an in vitro selectivity index (SI) of 8.0 vs. 0.01 for acyclovir. This complex also negatively influenced the expression of key structural HSV 1 proteins (VP23, gH and gG/gD), thus suppressing simultaneously virus entry, transactivation of virus genome, capsid assembly, and cell-to-cell spread of infectious HSV progeny.

Main structural and stereochemical aspects of the antiherpetic activity of nonahydroxyterphenoyl-containing C-glycosidic ellagitannins.

Antiherpetic evaluation of five nonahydroxyterphenoyl-containing C-glycosidic ellagitannins, castalagin (1), vescalagin (2), grandinin (3), roburin B (5), and roburin D (7), was performed in cultured cells against four HSV-1 and HSV-2 strains, two of which were resistant to Acyclovir. All five ellagitannins displayed significant anti-HSV activities against the Acyclovir-resistant mutants, but the monomeric structures 1-3 were more active than the dimers 5 and 7. Vescalagin (2) stands out among the five congeners tested as the most potent and selective inhibitor, with an IC50 value in the subfemtomolar range and a selectivity index 5x10(5) times higher than that of Acyclovir. Molecular modeling was used to provide a rationale for the surprisingly lower activity profile of its epimer castalagin (1). These ellagitannins have promising potential as novel inhibitors in the search for non-nucleoside drugs active against Acyclovir-resistant herpes viruses.