title: Leishmanicidal activity of synthetic chalcones in Leishmania (Viannia) braziliensis.
abstract: The treatment of American cutaneous leishmaniasis (ACL) is based on a small group of compounds that were developed decades ago, all of which are highly toxic and have a high rate of treatment failure. The chalcones show leishmanicidal activity, yet few studies have evaluated this activity against Leishmania (Viannia) braziliensis, one of the most important species of Leishmania across Latin America. Four new synthetic chalcones (1-4) were evaluated for inhibitory activity in vitro against promastigotes and intracellular parasites 24h post infection of L. (V.) braziliensis, cytotoxicity for macrophages J774.A1 and red blood cells, and the ability to stimulate nitric oxide production. The results for the inhibitory concentration for 50% of the promastigotes (IC50) (1.38±1.09-6.36±2.04μM), cytotoxic concentration for 50% of the macrophages (CC50) (13.49±3.13-199.43±4.11μM), and selectivity index (SI) (3.76 to 33.94) indicate that all chalcones (1-4) showed an effect on promastigotes of L. (V.) braziliensis; chalcone 2 had the highest SI. The haemolytic assay with chalcones 1 (301.93μM), 2 (534.18μM), 3 (419.46μM) and 4 (381.11μM) showed 0.00%, 2.33%, 0.57% and 1.74% haemolysis, respectively. All chalcones significantly reduced the infection index of macrophages by parasites; for chalcones (1-3) this effect may be dependent on nitric-oxide production by macrophages. The chalcones tested exhibited inhibitory activity for promastigotes and intracellular parasites of L. (V.) braziliensis, with low toxicity for macrophages and red blood cells. The anti-Leishmania activity of chalcones (1-3) may depend on the stimulation of nitric-oxide production in the initial stage of infection. These results show an initially encouraging potential for the use of chalcones (1-4) to treat ACL.
authors.affiliation: Post-Graduate Program in Health Sciences, Universidade Estadual de Maringá, Maringá, Brazil.
authors.forename: Tatiane F P
authors.initials: TF
authors.lastname: de Mello
authors.affiliation: Department of Chemistry, Universidade Federal do Pará, Belém, Brazil.
authors.forename: Heriberto R
authors.initials: HR
authors.lastname: Bitencourt
authors.affiliation: Post-Graduate Program in Health Sciences, Universidade Estadual de Maringá, Maringá, Brazil.
authors.forename: Raissa B
authors.initials: RB
authors.lastname: Pedroso
authors.affiliation: Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá, Maringá, Brazil.
authors.forename: Sandra M A
authors.initials: SM
authors.lastname: Aristides
authors.affiliation: Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá, Maringá, Brazil.
authors.forename: Maria V C
authors.initials: MV
authors.lastname: Lonardoni
authors.affiliation: Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá, Maringá, Brazil. Electronic address: tgvsilveira@uem.br.
authors.forename: Thais G V
authors.initials: TG
authors.lastname: Silveira
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D047188:Chalcones / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D006224:Cricetinae; D004912:Erythrocytes / Q000187:drug effects; D020128:Inhibitory Concentration 50; D007892:Leishmania braziliensis / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D047188:Chalcones; D009569:Nitric Oxide; D000666:Amphotericin B
keywords: Antiprotozoal; Chalcones; Cutaneous leishmaniasis; Leishmania braziliensis; Macrophages