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.
Gerpe
Alejandra
A
Departamento de Química Orgánica, Facultad de Química-Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, Uruguay.
Aguirre
Gabriela
G
Boiani
Lucía
L
Cerecetto
Hugo
H
González
Mercedes
M
Olea-Azar
Claudio
C
Rigol
Carolina
C
Maya
Juan D
JD
Morello
Antonio
A
Piro
Oscar E
OE
Arán
Vicente J
VJ
Azqueta
Amaia
A
de Ceráin
Adela López
AL
Monge
Antonio
A
Rojas
María Antonieta
MA
Yaluff
Gloria
G
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