title: In vitro antileishmanial and antitrypanosomal activities of flavanones from Baccharis retusa DC. (Asteraceae).
abstract: Leishmaniasis and Chagas' are parasitic protozoan diseases that affect the poorest population in the world, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, novel, safe and more efficacious drugs are essential. In this work, the CH(2)Cl(2) phase from MeOH extract from the leaves of Baccharis retusa DC. (Asteraceae) was fractioned to afford two flavonoids: naringenin (1) and sakuranetin (2). These compounds were in vitro tested against Leishmania spp. promastigotes and amastigotes and Trypanosoma cruzi trypomastigotes and amastigotes. Compound 2 presented activity against Leishmania (L.) amazonensis, Leishmania (V.) braziliensis, Leishmania (L.) major, and Leishmania (L.) chagasi with IC(50) values in the range between 43 and 52 μg/mL and against T. cruzi trypomastigotes (IC(50)=20.17 μg/mL). Despite of the chemical similarity, compound 1 did not show antiparasitic activity. Additionally, compound 2 was subjected to a methylation procedure to give sakuranetin-4'-methyl ether (3), which resulted in an inactive compound against both Leishmania spp. and T. cruzi. The obtained results indicated that the presence of one hydroxyl group at C-4' associated to one methoxyl group at C-7 is important to the antiparasitic activity. Further drug design studies aiming derivatives could be a promising tool for the development of new therapeutic agents for Leishmaniasis and Chagas' disease.
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP, Brazil.
authors.forename: Simone dos S
authors.initials: Sdos S
authors.lastname: Grecco
authors.forename: Juliana Q
authors.initials: JQ
authors.lastname: Reimão
authors.forename: André G
authors.initials: AG
authors.lastname: Tempone
authors.forename: Patricia
authors.initials: P
authors.lastname: Sartorelli
authors.forename: Rodrigo L O R
authors.initials: RL
authors.lastname: Cunha
authors.forename: Paulete
authors.initials: P
authors.lastname: Romoff
authors.forename: Marcelo J P
authors.initials: MJ
authors.lastname: Ferreira
authors.forename: Oriana A
authors.initials: OA
authors.lastname: Fávero
authors.forename: João Henrique G
authors.initials: JH
authors.lastname: Lago
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D031175:Baccharis / Q000737:chemistry*; D001681:Biological Assay; D006224:Cricetinae; D044950:Flavanones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D013329:Structure-Activity Relationship; D014345:Trypanosoma / Q000187:drug effects*; D000094162:Phytoalexins
chemical_list: D000981:Antiprotozoal Agents; D044950:Flavanones; D005419:Flavonoids; D010936:Plant Extracts; C099724:sakuranetin; D000094162:Phytoalexins; C005273:naringenin