Synthesis and evaluation of 1,1'-hydrocarbylenebis(indazol-3-ols) as potential antimalarial drugs.
Bis(indazol-3-ol) derivatives (5, 30-38) were prepared by alkylation of 3-alkoxyindazoles with alpha,omega-dibromides, followed by removal of the O-protecting groups. These compounds were subsequently evaluated as inhibitors of biocrystallization of ferriprotoporphyrin IX (heme) to hemozoin, a Plasmodium detoxification specific process. Most bis(5-nitroindazol-3-ols) were good inhibitors, however, a denitro analogue (38), the intermediate bis(3-alkoxyindazoles) (15-29) as well as bis(indazolin-3-ones) (39-42) were not active, showing the importance of the NO(2) and OH groups in the inhibition process.
Martins Alho
Miriam
M
CIHIDECAR (CONICET), Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina.
García-Sánchez
Rory N
RN
Nogal-Ruiz
Juan José
JJ
Escario
José Antonio
JA
Gómez-Barrio
Alicia
A
Martínez-Fernández
Antonio R
AR
Arán
Vicente J
VJ
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006420:Hemeproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006427:Hemin / Q000037:antagonists & inhibitors* / Q000737:chemistry; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects
D000962:Antimalarials; D006420:Hemeproteins; D007191:Indazoles; C020753:hemozoin; D006427:Hemin