Trypanocidal activity of Meliaceae and Rutaceae plant extracts

Abstract

(WHO 1997). Its treatment is still a challenge, since the only drug commercially available (benznidazole) possesses severe side effects and its activity is limited to the acute phase of the disease (De Castro 1993, Fairlamb 1999. Coura and De Castro (2002) mention that an effective chemotherapy is needed for the people who are already infected. The demonstration of parasites in chronic patients reinforces the need of finding more efficient and less toxic drugs.In the context of efforts to improve the therapy of Chagas disease, higher plants are a potential source of new drugs, with high activity and low toxicity (Phillipson & Wright 1991). Sepúlveda-Boza and Cassels (1996) mentioned a broad spectrum of chemical classes of substances showing activity against the parasite. Other promising compounds are the 2-aryl and 2-alkylquinoline alkaloids isolated from the extracts of the stem bark, root bark and leaves of Galipea longiflora (Rutaceae) (Fournet et al. 1994) and lignans from Zanthoxylum naranjillo (Rutaceae) (Bastos et al. 1999). In addition, we have been studying species of the order Rutales (Rutaceae, Meliaceae, Simaroubaceae, Burseraceae, and Cneoraceae) and several active substances have been isolated, mainly trypanocidal compounds (Mafezoli et al. 2000, Tomazela et al. 2000, Vieira et al. 2001.In this paper, we present the results of the trypanocidal activity of some extracts and fractions of Almeidea coerulea, Almeidea rubra, Conchocarpus heterophyllus, and Galipea carinata (from Rutaceae family), as well as Trichilia ramalhoi (from the family Meliaceae). Also, the results of the in vitro trypomastigote bioassay with flavone (1) and 7-methoxyflavone (2), the major compounds of one active fraction, are described. MATERIALS AND METHODSPlant material -All screened plants were collected in Southeastern Brazil, and identified by Dr José R Pirani from the Department of Botany, University of São Paulo, Brazil. The voucher herbarium specimens were deposited at the Herbarium of that Department (Table I).Preparation of crude extracts -Selected parts of the plants (leaves, stems, and/or branches) were dried carefully by forced air at 40°C and reduced to powder, followed by extraction three times with hexane by maceration at room temperature for 72 h. After the evaporation of the solvent under reduced pressure, crude hexane extracts were obtained. This process was repeated with methanol. The hexane and methanol extracts so obtained were assayed against T. cruzi.Fractionation of crude extracts -Methanol extracts of T. ramalhoi were fractionated through liquid-liquid partition with hexane-methanol-water, dichloromethanemethanol-water, ethyl acetate-methanol-water, and butanol-methanol-water. The crude extracts of A. coerulea, A. rubra, C. heterophyllus, G. carinata, and the hexane extract of the leaves of T. ramalhoi were submitted to vacuum liquid chromatography over silica gel using a gradient hexane, dichloromethane, ethyl acetate, and methanol, to yield the corresponding fractions, which were subsequently tested ...

Trypanocidal activity of flavonoids and limonoids isolated from Myrsinaceae and Meliaceae active plant extracts

“…Similar studies involving the trypanocidal activity of Meliaceae and Rutaceae species have been reported by our group (Mafezoli et al, 2000;Vieira et al, 2001;Ambrozin et al, 2004Ambrozin et al, , 2005aAmbrozin et al, , 2008 showing that these plants can be considered a promising source of active compounds against trypomastigote forms of T. cruzi. Thus, the significant results obtained from the extracts of C. fruticosa are consistent with those previously reported for this family.…”

“…The in vitro activity on T. cruzi of compounds 3 -6 is described herein. On the other hand, the activities of compounds 1, 2, 7 and 8 were previously reported (Ambrozin et al, 2004;Tasdemir et al, 2006).…”

“…The trypanocidal activity of flavone (7) and 7-methoxyflavone (8), isolated from the active hexane extract from branches of C. fruticosa (CFBH), was previously published by Ambrozin et al (2004). They showed that these flavonoids, isolated from an active fraction of Conchocarpus heterophyllus (Rutaceae), presented low activity against trypomastigote forms of T. cruzi (IC 50 = 2116 and 787 µg/mL or 9531 and 1084 µmol/L, respectively) when compared with other flavonoids (Ribeiro et al, 1997;Ambrozin et al, 2004).…”

“…They showed that these flavonoids, isolated from an active fraction of Conchocarpus heterophyllus (Rutaceae), presented low activity against trypomastigote forms of T. cruzi (IC 50 = 2116 and 787 µg/mL or 9531 and 1084 µmol/L, respectively) when compared with other flavonoids (Ribeiro et al, 1997;Ambrozin et al, 2004). Probably, the relevant activity obtained from the extract CFBH can be related to other characteristic metabolites of C. fruticosa.…”

“…Several extracts from plants of Meliaceae and Rutaceae families have been showed in vitro activity against T. cruzi (Mafezoli et al, 2000;Vieira et al, 2001;Ambrozin et al, 2004;de Mesquita et al, 2005). Therefore, natural products constitute a promising source of new active compounds for treatment of Chagas' disease.…”