In vitro and in vivo anthelmintic activity of (-)-6,6'-dinitrohinokinin against schistosomula and juvenile and adult worms of Schistosoma mansoni.

The chemotherapy of schistosomiasis relies on the use of praziquantel. However, concerns over drug resistance have encouraged the search for new drug leads. This paper is the first report on the in vitro and in vivo activity of (-)-6,6'-dinitrohinokinin (DNK) against Schistosoma mansoni. In vitro, the lethal concentrations for 50% of parasites (LC50) of DNK against adult worms were 103.9±3.6 and 102.5±4.8µM at 24 and 72h, respectively. Scanning electron microscopy images showed extensive tegumental alterations such as peeling and smaller numbers of tubercles in the spine of adult worms. DNK also elicited high mortality of schistosomula, with LC50 values of 57.4±2.3, 32.5±0.9, and 20.4±1.2µM at 24, 48, and 72h, respectively. DNK displayed moderate activity against the juvenile liver parasite, with an LC50 value of 179.5±2.3 µM at 72h. This compound reduced the total number of eggs by over 83%, and it affected the development of eggs produced by adult worms. The selectivity index showed that at 24h, DNK was 8.5 and 15.4 times more toxic to the adult worms and schistosomula than to Chinese hamster lung fibroblast cells, respectively. Treatment of infected mice with DNK moderately decreased worm burden (33.8-52.3%), egg production (40.7-60.0%), and spleen and liver weights. Together, our results indicated that DNK presents moderate in vitro and in vivo activities against S. mansoni, and it might therefore be interesting to explore the structure-activity relationship of the antischistosomal activity of this compound.

Antimicrobial activity of Rosmarinus officinalis against oral pathogens: relevance of carnosic acid and carnosol.

The in vitro inhibitory activity of crude EtOH/H2O extracts from the leaves and stems of Rosmarinus officinalis L. was evaluated against the following microorganisms responsible for initiating dental caries: Streptococcus mutans, S. salivarius, S. sobrinus, S. mitis, S. sanguinis, and Enterococcus faecalis. Minimum inhibitory concentrations (MIC) were determined with the broth microdilution method. The bioassay-guided fractionation of the leaf extract, which displayed the higher antibacterial activity than the stem extract, led to the identification of carnosic acid (2) and carnosol (3) as the major compounds in the fraction displaying the highest activity, as identified by HPLC analysis. Rosmarinic acid (1), detected in another fraction, did not display any activity against the selected microorganisms. HPLC Analysis revealed the presence of low amounts of ursolic acid (4) and oleanolic acid (5) in the obtained fractions. The results suggest that the antimicrobial activity of the extract from the leaves of R. officinalis may be ascribed mainly to the action of 2 and 3.