Mariela Risso

Synthesis and antitrypanosomal evaluation of E-isomers of 5-nitro-2-furaldehyde and 5-nitrothiophene-2-carboxaldehyde semicarbazone derivatives. Structure-activity relationships.

Several novel semicarbazone derivatives were prepared from 5-nitro-2-furaldehyde or 5-nitrothiophene-2-carboxaldehyde and semicarbazides bearing a spermidine-mimetic moiety. All derivatives presented the E-configuration, as determined by NMR-NOE experiments. These compounds were tested in vitro as potential antitrypanosomal agents, and some of them, together with the parent compounds, 5-nitro-2-furaldehyde and 5-nitrothiophene-2-carboxaldehyde semicarbazone derivatives, were also evaluated in vivo using infected mice. Structure-activity relationship studies were carried out using voltammetric response and lipophilic-hydrophilic balance as parameters. Two of the compounds (1 and 3) displayed the highest in vivo activity. A correlation was found between lipophilic-hydrophilic properties and trypanocidal activity, high R(M) values being associated with low in vivo effects.

1,2,5-Oxadiazole N-oxide derivatives as potential anti-cancer agents: synthesis and biological evaluation. Part IV

Several new 1,2,5-oxadiazole N-oxide derivatives and some deoxygenated analogues were synthesized to be tested as potential selective hypoxic cell cytotoxins. Compounds prepared were designed in order to gain insight into the mechanism of action of this kind of cytotoxin. Compounds were tested in oxia and hypoxia and they proved to be non-selective. 3-Cyano-N(2)-oxide-4-phenyl-1,2,5-oxadiazole showed the best cytotoxic activity in oxia. The cytotoxicity observed for these derivatives could be explained in terms of the electronic characteristics of the 1,2,5-oxadiazole substituents. Electrochemical and ESR studies were performed on the more cytotoxic derivative.

Electrochemical and microsomal production of free radicals from 1,2,5-oxadiazole N-oxide as potential antiprotozoal drugs

The electron spin resonance (ESR) spectra of free radicals obtained by electrolytic or microsomal reduction of several potential antiprotozoal 1,2,5-oxadiazoles were characterized and analyzed. Ab initio molecular orbital calculations were performed to obtain the optimized geometries and the theoretical hyperfine constant was carried out using ZINDO semiempirical methodology. Density functional theory was used to rationalize the reduction potentials of these compounds.

Microwave-assisted solvent-free lipase catalyzed transesterification of β-ketoesters

Abstract Lipase-catalyzed transesterification was used as an efficient tool for the interconversion of β-ketoesters. Catalytic activity of commercial lipase B from Candida antarctica (Novozym 435) was evaluated in systems involving non activated acyl donors, and enhanced using microwave irradiation. Interestingly, the combination of CAL B in microwave irradiation worked excellent in solvent-free conditions, thus assuring a highly competitive and environment-friendly process with high yields (up to 96%) in competitive times (< 2h). The combination of biocatalysis with solvent-free systems and microwave assistance is currently scarcely used, and may represent a powerful synergy for preparative reactions.

Synthesis and biological evaluation of 1,2,5-oxadiazole N-oxide derivatives as potential hypoxic cytotoxins and DNA-binders.

Several new 1,2,5‐oxadiazole N‐oxide derivatives were synthesized to be tested both as potential selective hypoxic cell cytotoxins and as DNA‐binding agents. The compounds prepared included bis(1,2,5‐oxadiazole N‐oxide) derivatives and oxadiazole rings linked to naphthyl residues. The compounds were tested for their cytotoxicity in oxia and hypoxia and they proved to be non‐selective and less active than the parent compounds 3‐formyl‐4‐phenyl‐1,2,5‐oxadiazole N2‐oxide (3) and 3‐chloromethyl‐4‐phenyl‐1,2,5‐oxadiazole N2‐oxide (4). The DNA‐affinity assays showed that the compounds tested have poor affinity for this biomolecule.

Chemical Modifications of 1,2,5-Oxadiazole N-Oxide System Searching for Cytotoxic Selective Hypoxic Drugs

New analogues of 3-Formyl-4-phenyl-1,2,5-oxadiazole N-oxide (1) are prepared and evaluated as cytotoxic selective agents in hypoxia.