title: Synthesis and antileishmanial activities of novel 3-substituted quinolines.
abstract: 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.
authors.affiliation: 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
authors.forename: André Gustavo
authors.initials: AG
authors.lastname: Tempone
authors.forename: Ana Cláudia Melo Pompeu
authors.initials: AC
authors.lastname: da Silva
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Brandt
authors.forename: Fernanda Scalzaretto
authors.initials: FS
authors.lastname: Martinez
authors.forename: Samanta Etel Treiger
authors.initials: SE
authors.lastname: Borborema
authors.forename: Maria Amélia Barata
authors.initials: MA
authors.lastname: da Silveira
authors.forename: Heitor Franco
authors.initials: HF
authors.lastname: de Andrade
mesh_terms: 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
chemical_list: D000981:Antiprotozoal Agents; D011804:Quinolines; D009569:Nitric Oxide
references.citation: Int J Clin Lab Res. 1999;29(3):122-7
references.pmid: 10592110
references.citation: JAMA. 1999 Jan 27;281(4):361-7
references.pmid: 9929090
references.citation: Antimicrob Agents Chemother. 2001 Apr;45(4):1121-5
references.pmid: 11257025
references.citation: Antimicrob Agents Chemother. 2001 Jun;45(6):1886-8
references.pmid: 11353644
references.citation: Trop Med Int Health. 2001 Nov;6(11):945-51
references.pmid: 11703850
references.citation: Am J Trop Med Hyg. 2001 Dec;65(6):685-9
references.pmid: 11791957
references.citation: Bioorg Med Chem. 2002 Jun;10(6):1687-93
references.pmid: 11937327
references.citation: Curr Opin Investig Drugs. 2002 Apr;3(4):538-44
references.pmid: 12090720
references.citation: Curr Opin Investig Drugs. 2002 Oct;3(10):1446-52
references.pmid: 12431016
references.citation: BMJ. 2003 Feb 15;326(7385):377-82
references.pmid: 12586674
references.citation: Mem Inst Oswaldo Cruz. 2003 Jan;98(1):145-9
references.pmid: 12700873
references.citation: Biochem Biophys Res Commun. 2004 Apr 30;317(2):639-47
references.pmid: 15063806
references.citation: J Antimicrob Chemother. 2004 Jul;54(1):60-8
references.pmid: 15163652
references.citation: Antimicrob Agents Chemother. 1985 Dec;28(6):723-6
references.pmid: 3002244
references.citation: J Immunol Methods. 1986 Nov 6;93(2):157-65
references.pmid: 3490518
references.citation: Braz J Med Biol Res. 1987;20(6):665-74
references.pmid: 3331952
references.citation: Ultrastruct Pathol. 1992 Jul-Aug;16(4):475-82
references.pmid: 1502740
references.citation: World Health Stat Q. 1992;45(2-3):267-75
references.pmid: 1462660
references.citation: Antimicrob Agents Chemother. 1996 Nov;40(11):2447-51
references.pmid: 8913444
references.citation: J Antimicrob Chemother. 1996 Dec;38(6):1041-7
references.pmid: 9023651
references.citation: Exp Parasitol. 1997 Oct;87(2):98-111
references.pmid: 9326885
references.citation: Gen Pharmacol. 1998 Apr;30(4):435-43
references.pmid: 9580315
references.citation: Biochem Biophys Res Commun. 2001 Jan 26;280(3):620-4
references.pmid: 11162565