title: Synthesis, β-hematin inhibition studies and antimalarial evaluation of dehydroxy isotebuquine derivatives against Plasmodium berghei.
abstract: Diverse dehydroxy-isotebuquine derivatives were prepared by using a five step synthetic sequence in good yields. All these new 4-aminoquinolines were evaluated as inhibitors of haemozoin formation, where most of them showed a significant inhibition value (% IHF >97). The best inhibitors were tested in vivo as potential antimalarials in mice infected with Plasmodium berghei ANKA chloroquine susceptible strain, three of them (11b, 11d and 11h) displayed an antimalarial activity comparable to that of chloroquine.
authors.affiliation: Laboratorio de Química Medicinal y Heterociclos, Departamento de Química, Universidad Simón Bolívar, Valle de Sartenejas, Baruta, Caracas 1080-A, Apartado 89000, Venezuela.
authors.forename: Angel H
authors.initials: AH
authors.lastname: Romero
authors.affiliation: Unidad de Bioquímica, Facultad de Farmacia, Universidad Central de Venezuela, Los Chaguaramos, Caracas, Venezuela.
authors.forename: María E
authors.initials: ME
authors.lastname: Acosta
authors.affiliation: Unidad de Bioquímica, Facultad de Farmacia, Universidad Central de Venezuela, Los Chaguaramos, Caracas, Venezuela.
authors.forename: Neira
authors.initials: N
authors.lastname: Gamboa
authors.affiliation: Laboratorio de Síntesis Orgánica, Facultad de Farmacia, Universidad Central de Venezuela, Los Chaguaramos, 1041-A Caracas, Venezuela.
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Charris
authors.affiliation: Laboratorio de Química Medicinal y Heterociclos, Departamento de Química, Universidad Simón Bolívar, Valle de Sartenejas, Baruta, Caracas 1080-A, Apartado 89000, Venezuela.
authors.forename: José
authors.initials: J
authors.lastname: Salazar
authors.affiliation: Laboratorio de Química Medicinal y Heterociclos, Departamento de Química, Universidad Simón Bolívar, Valle de Sartenejas, Baruta, Caracas 1080-A, Apartado 89000, Venezuela. Electronic address: slopez@usb.ve.
authors.forename: Simón E
authors.initials: SE
authors.lastname: López
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006420:Hemeproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008288:Malaria / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D006420:Hemeproteins; C020753:hemozoin; C044651:tebuquine; D002738:Chloroquine
keywords: 4-Aminoquinoline; Antimalarial activity; Haemozoin formation; Isotebuquine; Malaria; β-Hematin