Complexation of new Thiosemicarbazone based anti-viral agents for the evaluation of the biological activity

GLISONI R.J.; CHIAPPETTA D.A.; MOGLIONI A.G.; SOSNIK A.

Santa Fé, Argentina

Congreso; 1º Taller de Órganos Artificiales, Biomateriales e Ingeniería de Tejidos. BIOOMAT 2009.; 2009

Thiosemicarbazones (TSCs) have been evaluated as therapeutic agents since 1946, when their activity against Mycobacterium tuberculosis was reported for the first time. Since then, this and other biological properties of TSC derivatives such as antibacterial, antitumoral, antiprotozoal, and antiviral have been described. Some TSCs like ambazone, metisazone and triapine have been approved by FDA to treatment of diseases such as viral infections and leukemias. Our research group, has reported the inhibitory activity of TSCs synthesized from aromatic ketones and terpenones1 against Junin virus (JUNV), causative agent of Argentine hemorrhagic fever (AHF). Among them, 1-indanone TSC derivatives with different patterns of substitution in the aromatic ring. These derivatives (Fig.1), are poorly water-soluble and show an amphiphilic character that would result in their gradual self-aggregation in water. This behavior dramatically constrained the biological tests in vitro; these assays are carried out by solubilizing TSCs in dimethyl sulfoxide (DMSO) and then adding the organic solution to the culture medium. Therefore, the maximal TSCs concentration attainable in culture is determined by the cytotoxicity of DMSO. In this context, it is important to design an appropriate vehicle to improve the solubility of these new drug candidates as an essential stage prior to the exhaustive analysis of the antiviral activity. Cyclodextrins (CDs) (Fig. 2) are cyclic α-(1,4)-linked oligosaccharides of α-D-glucopyranose containing a relatively hydrophobic nano-cavity and a hydrophilic outer surface. The hydrophobic cavity enables the partial or total incorporation of lipophilic molecules