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-furald ehyde or 5-nitrothiophene-2-carboxaldehyde and semicarbazides bearing a spe rmidine-mimetic moiety. All derivatives presented the E-configuration, as d etermined by NMR-NOE experiments. These compounds were tested in vitro as p otential antitrypanosomal agents, and some of them, together with the paren t compounds, 5-nitro-2-furaldehyde and 5-nitrothiophene-2-carboxaldehyde se micarbazone derivatives, were also evaluated in vivo using infected mice. S tructure-activity relationship studies were carried out using voltammetric response and lipophilic-hydrophilic balance as parameters. Two of the compo unds (1 and 3) displayed the highest in vivo activity. A correlation was fo und between lipophilic-hydrophilic properties and trypanocidal activity, hi gh R-M values being associated with low in vivo effects. (C) 2000 Editions scientifiques et medicales Elsevier SAS.