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.
Cerecetto
H
H
Departamento de Química Organica, Facultad de Química, Universidad de la República, CC 1157, 11800-Montevideo, Uruguay. hcerecet@bilbo.edu.uy
Di Maio
R
R
González
M
M
Risso
M
M
Sagrera
G
G
Seoane
G
G
Denicola
A
A
Peluffo
G
G
Quijano
C
C
Stoppani
A O
AO
Paulino
M
M
Olea-Azar
C
C
Basombrío
M A
MA
D000447:Aldehydes / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy / Q000469:parasitology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D004563:Electrochemistry; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects
C409455:5-nitrothiophene-2-carboxaldehyde; D000447:Aldehydes; D008055:Lipids; D013438:Sulfhydryl Compounds; D014344:Trypanocidal Agents; D005662:Furaldehyde; C052590:5-nitro-2-furaldehyde