Details

Autor(en) / Beteiligte

• Boechat, Núbia
• Ferreira, Maria de Lourdes G.
• Pinheiro, Luiz C. S.
• Jesus, Antônio M. L.
• Leite, Milene M. M.
• Júnior, Carlos C. S.
• Aguiar, Anna C. C.
• de Andrade, Isabel M.
• Krettli, Antoniana U.

Titel

New Compounds Hybrids 1H-1,2,3-Triazole-Quinoline Against Plasmodium falciparum

Ist Teil von

• Chemical biology & drug design, 2014-09, Vol.84 (3), p.325-332

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2014

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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). Chloroquine (CQ) is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of CQ‐resistant strains. 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 with IC50 values ranging from 1.4 to 46 µm.