Luiz E. Gregório

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).

Anticariogenic properties of ent-pimarane diterpenes obtained by microbial transformation.

In the present work, the anticariogenic activities of three pimarane-type diterpenes obtained by fungal biotransformation were investigated. Among these metabolites, ent-8(14),15-pimaradien-19-ol was the most active compound, displaying very promising MIC values (ranging from 1.5 to 4.0 μg mL−1) against the main microorganisms responsible for dental caries: Streptococcus salivarius, S. sobrinus, S. mutans, S. mitis, S. sanguinis, and Lactobacillus casei. Time kill assays performed with ent-8(14),15-pimaradien-19-ol against the primary causative agent S. mutans revealed that this compound only avoids growth of the inoculum in the first 12 h (bacteriostatic effect). However, its bactericidal effect is clearly noted thereafter (between 12 and 24 h). The curve profile obtained by combining ent-8(14),15-pimaradien-19-ol and chlorhexidine revealed a significant reduction in the time necessary for killing S. mutans compared with each of these two chemicals alone. However, no synergistic effect was observed using the same combination in the checkerboard assays against this microorganism. In conclusion, our results point out that ent-8(14),15-pimaradien-19-ol is an important metabolite in the search for new effective anticariogenic agents.

Fungal Transformation and Schistosomicidal Effects of Pimaradienoic Acid

The schistosomicidal effects of pimaradienoic acid (PA) and two derivatives, obtained by fungal transformation in the presence of Aspergillus ochraceus, were investigated. PA was the only compound with antischistosomal activity among the three diterpenes studied, with the ability to significantly reduce the viability of the parasites at concentrations ranging from 25 to 100 μM. PA also promoted morphological alterations of the tegument of Schistosoma mansoni, separated all the worm couples, and affected the production and development of eggs. Moreover, this compound was devoid of toxicity toward human fibroblasts. In a preliminary in vivo experiment, PA at a dose of 100 mg/kg significantly diminished the number of parasites in infected Balb/c mice. Taken together, these results show that PA may be potentially employed in the discovery of novel schistosomicidal agents, and that diterpenes are an important class of natural compounds for the investigation of agents capable of fighting the parasite responsible for human schistosomiasis.

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.

Chemical Constituents of the Ethanolic Extract of Mikania parodii

CEP 14040-901, Ribeirao Preto, SP, Brazil; 2) Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Via do Cafe s/n, CEP 14040-903, Ribeirao Preto, SP, Brazil, fax: +55 16 3602 4243, e-mail: drolivei@fcfrp.usp.br; 3) Centro Nacional de Pesquisa e Gado de Corte–CNPGC/EMBRAPA, Rodovia BR-262, km-04, Caixa Postal 154, CEP 79002970 Campo Grande, MS, Brazil. Published in Khimiya Prirodnykh Soedinenii, No. 4, p. 413, July-August, 2008. Original article submitted February 12, 2007.