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

• Published in: European journal of medicinal chemistry 2000-03, Vol.35 (3), p.343-350
• Main Authors: Cerecetto, Hugo, Di Maio, Rossanna, González, Mercedes, Risso, Mariela, Sagrera, Gabriel, Seoane, Gustavo, Denicola, Ana, Peluffo, Gonzalo, Quijano, Celia, Stoppani, Andrés O.M, Paulino, Margot, Olea-Azar, Claudio, Basombrío, Miguel Angel
• Format: Article
• Language: English
• Subjects: 5-nitrofurfural and 5-nitrothiophene-2-carboxaldehyde semicarbazones; Aldehydes - chemical synthesis; Aldehydes - pharmacology; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; antitrypanosomal activity; Biological and medical sciences; Chagas Disease - drug therapy; Chagas Disease - parasitology; Chemical Phenomena; Chemistry, Physical; Chromatography, Thin Layer; Electrochemistry; Furaldehyde - analogs & derivatives; Furaldehyde - chemical synthesis; Furaldehyde - pharmacology; in vivo evaluation; Lipids - chemistry; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Medical sciences; Mice; Pharmacology. Drug treatments; Spectrophotometry, Infrared; Structure-Activity Relationship; Sulfhydryl Compounds - chemical synthesis; Sulfhydryl Compounds - pharmacology; Trypanocidal Agents - chemical synthesis; Trypanocidal Agents - pharmacology; Trypanosoma cruzi - drug effects
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/S0223-5234(00)00131-8

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.