Indazole N-oxide derivatives as antiprotozoal agents: synthesis, biological evaluation and mechanism of action studies.
A series of indazole N-oxide derivatives have been synthesized and their antichagasic and leishmanocidal properties studied. 3-Cyano-2-(4-iodophenyl)-2H-indazole N1-oxide exhibited interesting antichagasic activity on the two parasitic strains and the two parasitic stages evaluated. Furthermore, besides its trypanocidal activity, 3-cyano-2-(4-nitrophenyl)-2H-indazole N1-oxide showed leishmanocidal activity in the three parasitic strains evaluated. To gain insight into the mechanism of action, electrochemical behaviour, ESR experiment, inhibition of parasitic respiration and QSAR were performed.
Departamento de Química Orgánica, Facultad de Química-Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, Uruguay.
Alejandra
A
Gerpe
Gabriela
G
Aguirre
Lucía
L
Boiani
Hugo
H
Cerecetto
Mercedes
M
González
Claudio
C
Olea-Azar
Carolina
C
Rigol
Juan D
JD
Maya
Antonio
A
Morello
Oscar E
OE
Piro
Vicente J
VJ
Arán
Amaia
A
Azqueta
Adela López
AL
de Ceráin
Antonio
A
Monge
María Antonieta
MA
Rojas
Gloria
G
Yaluff
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007891:Leishmania / Q000187:drug effects; D008958:Models, Molecular; D021261:Parasitic Sensitivity Tests; D021281:Quantitative Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000187:drug effects
D000970:Antineoplastic Agents; D000981:Antiprotozoal Agents; D007191:Indazoles