title: Synthesis and evaluation of 1,1'-hydrocarbylenebis(indazol-3-ols) as potential antimalarial drugs.
abstract: 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.
authors.affiliation: CIHIDECAR (CONICET), Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina.
authors.forename: Miriam
authors.initials: M
authors.lastname: Martins Alho
authors.forename: Rory N
authors.initials: RN
authors.lastname: García-Sánchez
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Nogal-Ruiz
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Escario
authors.forename: Alicia
authors.initials: A
authors.lastname: Gómez-Barrio
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Martínez-Fernández
authors.forename: Vicente J
authors.initials: VJ
authors.lastname: Arán
mesh_terms: 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
chemical_list: D000962:Antimalarials; D006420:Hemeproteins; D007191:Indazoles; C020753:hemozoin; D006427:Hemin