Synthesis and biological properties of new 5-nitroindazole derivatives.
A series of new 3-alkoxy- or 3-hydroxy-1-[omega-(dialkylamino)alkyl]-5-nitroindazoles have been synthesized and their trichomonacidal, antichagasic and antineoplastic properties studied. Five derivatives (5, 6, 8, 9 and 17) showed remarkable trichomonacidal activity against Trichomonas vaginalis at 10 microg/mL concentration. Three compounds (8, 10, 11) exhibited interesting antichagasic activity and these same compounds moderate antineoplastic activity against TK-10 and HT-29 cell lines. Unspecific cytotoxicity against macrophages has also been evaluated and only compounds 9, 10 and 11 resulted cytotoxic at the higher dose evaluated (100 microg/mL), loosing cytotoxicity at lower doses. QSAR studies have been carried out. X-ray crystallographic study of compound 8 has been performed.
Arán
Vicente J
VJ
Instituto de Química Médica, Juan de la Cierva 3, 28006 Madrid, Spain. vjaran@iqm.csic.es
Ochoa
Carmen
C
Boiani
Lucía
L
Buccino
Pablo
P
Cerecetto
Hugo
H
Gerpe
Alejandra
A
González
Mercedes
M
Montero
David
D
Nogal
Juan José
JJ
Gómez-Barrio
Alicia
A
Azqueta
Amaya
A
López de Ceráin
Adela
A
Piro
Oscar E
OE
Castellano
Eduardo E
EE
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000994:Antitrichomonal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D021281:Quantitative Structure-Activity Relationship; D014246:Trichomonas vaginalis / Q000187:drug effects; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects
D000970:Antineoplastic Agents; D000994:Antitrichomonal Agents; D007191:Indazoles; D014344:Trypanocidal Agents