Synthesis and antileishmanial activities of novel 3-substituted quinolines.
The antileishmanial efficacy of four novel quinoline derivatives was determined in vitro against Leishmania chagasi, using extracellular and intracellular parasite models. When tested against L. chagasi-infected macrophages, compound 3b demonstrated 8.3-fold greater activity than did the standard pentavalent antimony. No significant activity was found for compounds 3a, 4a, and 4b. The antilesihmanial effect of compound 3b was independent of host cell activation, as demonstrated by nitric oxide production. Ultrastructural studies of promastigotes treated with compound 3b showed mainly enlarged mitochondria, with matrix swelling and reduction in the number of cristae. Synthetic analogues based on the quinoline ring structure, already an established template for antiparasitic drugs, could provide further useful compounds.
Tempone
André Gustavo
AG
Laboratorio de Parasitologia, Divisao de Biologia Medica, Instituto Adolfo Lutz, Av. Dr. Arnaldo 355, 8 degree andar CEP, 01246-000 Sao Paulo, Brazil. atempone@ial.sp.gov.br
da Silva
Ana Cláudia Melo Pompeu
AC
Brandt
Carlos Alberto
CA
Martinez
Fernanda Scalzaretto
FS
Borborema
Samanta Etel Treiger
SE
da Silveira
Maria Amélia Barata
MA
de Andrade
Heitor Franco
HF
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D007891:Leishmania / Q000187:drug effects* / Q000648:ultrastructure; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D011804:Quinolines; D009569:Nitric Oxide
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