Aa Da Silva Filho

In vitro antileishmanial, antiplasmodial and cytotoxic activities of phenolics and triterpenoids from Baccharis dracunculifolia D. C. (Asteraceae)

Baccharis dracunculifolia (Asteraceae), the most important plant source of the Brazilian green propolis (GPE), displayed in vitro activity against Leishmania donovani, with an IC(50) value of 45 microg/mL, while GPE presented an IC(50) value of 49 microg/mL. Among the isolated compounds of B. dracunculifolia, ursolic acid, and hautriwaic acid lactone showed IC(50) values of 3.7 microg/mL and 7.0 microg/mL, respectively. Uvaol, acacetin, and ermanin displayed moderate antileishmanial activity. Regarding the antiplasmodial assay against Plasmodium falciparum, BdE and GPE gave similar IC(50) values (about 20 microg/mL), while Hautriwaic acid lactone led to an IC(50) value of 0.8 microg/mL (D6 clone).

Antibacterial activity of triterpene acids and semi-synthetic derivatives against oral pathogens.

Triterpene acids (ursolic, oleanoic, gypsogenic, and sumaresinolic acids) isolated from Miconia species, along with a mixture of ursolic and oleanolic acids and a mixture of maslinic and 2-α-hydroxyursolic acids, as well as ursolic acid derivatives were evaluated against the following microorganisms: Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, Streptococcus salivarius, Streptococcus sobrinus, and Enterococcus faecalis, which are potentially responsible for the formation of dental caries in humans. The microdilution method was used for the determination of the minimum inhibitory concentration (MIC) during the evaluation of the antibacterial activity. All the isolated compounds, mixtures, and semi-synthetic derivatives displayed activity against all the tested bacteria, showing that they are promising antiplaque and anticaries agents. Ursolic and oleanolic acids displayed the most intense antibacterial effect, with MIC values ranging from 30 μg/mL to 80 μg/mL. The MIC values of ursolic acid derivatives, as well as those obtained for the mixture of ursolic and oleanolic acids showed that these compounds do not have higher antibacterial activity when compared with the activity observed with either ursolic acid or oleanolic acid alone. With regard to the structure-activity relationship of triterpene acids and derivatives, it is suggested that both hydroxy and carboxy groups present in the triterpenes are important for their antibacterial activity against oral pathogens.

Schistosomicidal and trypanocidal structure-activity relationships for (+/-)-licarin A and its (-)- and (+)-enantiomers

(±)-Licarin A (1) was obtained by oxidative coupling, and its enantiomers, (-)-licarin A (2) and (+)-licarin A (3), were resolved by chiral HPLC. Schistosomicidal and trypanocidal activities of these compounds were evaluated in vitro against Schistosoma mansoni adult worms and trypomastigote forms of Trypanosoma cruzi. The racemic mixture (1) displayed significant schistosomicidal activity with an LC₅₀ value of 53.57 μM and moderate trypanocidal activity with an IC₅₀ value of 127.17 μM. On the other hand, the (-)-enantiomer (2), displaying a LC₅₀ value of 91.71 μM, was more active against S. mansoni than the (+)-enantiomer (3), which did not show activity. For the trypanocidal assay, enantiomer 2 showed more significant activity (IC₅₀ of 23.46 μM) than enantiomer 3, which showed an IC₅₀ value of 87.73 μM. Therefore, these results suggest that (±)-licarin A (1) and (-)-licarin A (2) are promising compounds that could be used for the development of schistosomicidal and trypanocidal agents.

Constituents of Baccharis dracunculifolia DC (Asteraceae) with in vitro antileishmanial, antiplasmodial and cytotoxic activities

Baccharis dracunculifolia D.C. (Asteraceae) is the most important plant source of the Brazilian green propolis. The aim of this work was to evaluate the antileishmanial and antiplasmodial activities of B. dracunculifolia and its isolated compounds. The leave rinse extract of B. dracunculifolia (BdE) showed in vitro antileishmanial activity against Leishmania donovani, displaying an IC50 value of 45µg/mL, while green propolis hydroalcoholic extract (GPE) showed an IC50 value of 49µg/mL. Among the isolated compounds, ursolic acid and hautriwaic acid lactone, showed the highest antileishmanial activities, displaying IC50 values of 3.7µg/mL and 7.0µg/mL, respectively. The pentacyclic triterpene Uvaol, as well as the flavonoids acacetin and ermanin showed IC50 values of 15.0µg/mL, 18.0µg/mL and 40.0µg/mL, respectively. Regarding the antiplasmodial assay against Plasmodium falciparum, BdE and GPE showed similar IC50 values (about 20µg/mL). Hautriwaic acid lactone displayed moderate antiplasmodial activity, with IC50 values of 0.8µg/mL (D6 clone) and 2.2µg/mL (W2 clone). In order to compare the effect on the parasites with toxicity with mammalian cells, the cytotoxic activity of the samples were evaluated against the Vero cells, showing that all evaluated compounds exhibited no cytotoxicity in the maximum dose tested. Acknowledgements: To FAPESP for financial support (2006/60142–4) and FAPESP (2007/04175–9, CAPES (PDEE/BEX 0387/04–5) and CNPq (119831/2007–4) for fellowships.