title: New compounds hybrids 1h-1,2,3-triazole-quinoline against Plasmodium falciparum.
abstract: Malaria is one of the most prevalent parasitic diseases in the world. The global importance of this disease, current vector control limitations, and the absence of an effective vaccine make the use of therapeutic antimalarial drugs the main strategy to control malaria. Chloroquine is a cost-effective antimalarial drug with a relatively robust safety profile, or therapeutic index. However, chloroquine is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of chloroquine-resistant strains, which have also been reported for Plasmodium vivax. However, the activity of 1,2,3-triazole derivatives against chloroquine-sensitive and chloroquine-resistant strains of P. falciparum has been reported in the literature. To enhance the anti-P. falciparum activity of quinoline derivatives, we synthesized 11 new quinoline-1H-1,2,3-triazole hybrids with different substituents in the 4-positions of the 1H-1,2,3-triazole ring, which were assayed against the W2-chloroquine-resistant P. falciparum clone. Six compounds exhibited activity against the P. falciparum W2 clone, chloroquine-resistant, with IC50 values ranging from 1.4 to 46 μm. None of these compounds was toxic to a normal monkey kidney cell line, thus exhibiting good selectivity indexes, as high 351 for one compound (11).
authors.affiliation: Departamento de Síntese de Fármacos, Instituto de Tecnologia em Fármacos - Farmanguinhos, FIOCRUZ, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, RJ, 21041-250, Brazil.
authors.forename: Núbia
authors.initials: N
authors.lastname: Boechat
authors.forename: Maria de Lourdes G
authors.initials: Mde L
authors.lastname: Ferreira
authors.forename: Luiz C S
authors.initials: LC
authors.lastname: Pinheiro
authors.forename: Antônio M L
authors.initials: AM
authors.lastname: Jesus
authors.forename: Milene M M
authors.initials: MM
authors.lastname: Leite
authors.forename: Carlos C S
authors.initials: CC
authors.lastname: Júnior
authors.forename: Anna C C
authors.initials: AC
authors.lastname: Aguiar
authors.forename: Isabel M
authors.initials: IM
authors.lastname: de Andrade
authors.forename: Antoniana U
authors.initials: AU
authors.lastname: Krettli
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance / Q000187:drug effects; D004912:Erythrocytes / Q000469:parasitology; D000882:Haplorhini; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects / Q000502:physiology*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000962:Antimalarials; D011804:Quinolines; D014230:Triazoles; D002738:Chloroquine; C037219:quinoline
keywords: Antiplasmodial; Plasmodium falciparum; hybrids; quinoline; triazole