In Vitro Schistosomicidal Activity of Balsaminol F and Karavilagenin C

Five cucurbitane-type triterpenes (1-5), previously isolated from the African medicinal plant Momordica balsamina, along with five ester derivatives (6-10) of karavilagenin C (2), were evaluated for their potential schistosomicidal activity against Schistosoma mansoni adult worms. The natural compounds were isolated from the ethyl acetate-soluble fraction of the methanol extract of the aerial parts of M. balsamina. In a preliminary study, a significant schistosomicidal activity was observed for both the crude methanol extract and the ethyl acetate fraction. The compounds responsible for the activity were found to be balsaminol F (1) and karavilagenin C (2) with LC50 values of 14.7 +/- 1.5 and 28.9 +/- 1.8 mu M, respectively, after 24 h of incubation (positive control praziquantel, LC50 = 1.2 +/- 0.1 mu M). Both compounds (1, 2), at 10-50 mu M, induced significant reductions in the motor activity of the worms and significantly decreased the egg production. Furthermore, they were able (at 10-100 mu M) to separate the adult worm pairs into male and female after 24 h. Compounds 3-5, bearing a sugar moiety as a substituent, and the acylated derivatives of karavilagenin C (6-10) were inactive, suggesting that the presence of free hydroxyl groups in the tetracyclic skeleton might be important for the activity. A correlation between activity and the molecular volume/weight of compounds was also found.

In Vitro Schistosomicidal Activity of Some Brazilian Cerrado Species and Their Isolated Compounds

Miconia langsdorffii Cogn. (Melastomataceae), Roupala montana Aubl. (Proteaceae), Struthanthus syringifolius (Mart.) (Loranthaceae), and Schefflera vinosa (Cham. & Schltdl.) Frodin (Araliaceae) are plant species from the Brazilian Cerrado whose schistosomicidal potential has not yet been described. The crude extracts, fractions, the triterpenes betulin, oleanolic acid, ursolic acid and the flavonoids quercetin 3-O-beta-D-rhamnoside, quercetin 3-O-beta-D-glucoside, quercetin 3-O-beta-D-glucopyranosyl-(1-2)-alpha-L-rhamnopyranoside and isorhamnetin 3-O-beta-D-glucopyranosyl-(1-2)-alpha-L-rhamnopyranoside were evaluated in vitro against Schistosoma mansoni adult worms and the bioactive n-hexane fractions of the mentioned species were also analyzed by GC-MS. Betulin was able to cause worm death percentage values of 25% after 120 h (at 100 mu M), and 25% and 50% after 24 and 120 h (at 200 mu M), respectively; besides the flavonoid quercetin 3-O-beta-D-rhamnoside promoted 25% of death of the parasites at 100 mu M. Farther the flavonoids quercetin 3-O-beta-D-glucoside and quercetin 3-O-beta-D-rhamnoside at 100 mu M exhibited significantly reduction in motor activity, 75% and 87.5%, respectively. Biological results indicated that crude extracts of R. montana, S. vinosa, and M. langsdorffii and some n-hexane and EtOAc fractions of this species were able to induce worm death to some extent. The results suggest that lupane-type triterpenes and flavonoid monoglycosides should be considered for further antiparasites studies.

Susceptibilities of the dermatophytes Trichophyton mentagrophytes and T. rubrum microconidia to photodynamic antimicrobial chemotherapy with novel phenothiazinium photosensitizers and red light

Photodynamic antimicrobial chemotherapy (PACT) is a promising alternative to conventional chemotherapy that can be used to treat localized mycosis. The development of PACT depends on identifying effective and selective PS for the different pathogenic species. The in vitro susceptibilities of Trichophyton mentagrophytes and Trichophyton rubrum microconidia to PACT with methylene blue (MB), toluidine blue o (TBO), new methylene blue N (NMBN), and the novel pentacyclic phenothiazinium photosensitizer S137 were investigated. The efficacy of each PS was determined based on its minimal inhibitory concentration (MIC). Additionally, we evaluated the effect of PACT with NMBN and S137 on the survival of the microconidia of both species. 5137 showed the lowest MIC. MIC for S137 was 2.5 mu M both for T. mentagrophytes and T. rubrum, when a light dose of 5J cm(-2) was used. PACT with NMBN (10 mu M and 20J cm(-2)) resulted in a reduction of 4 logs in the survival of the T. rubrum and no survivor of T. mentagrophytes was observed. PACT with S137 at 1 mu M and 20J cm(-2) resulted in a reduction of approximately 3 logs in the survival of both species. When a S137 concentration of 10 mu M was used, no survivor was observed for both species at all light doses (5, 10 and 20J cm(-2)). (C) 2012 Elsevier B.V. All rights reserved.

Exploration of the Antiplatelet Activity Profile of Betulinic Acid on Human Platelets

Betulinic acid, a natural pentacyclic triterpene acid, presents a diverse mode of biological actions including antiretroviral, antibacterial, antimalarial, and anti-inflammatory activities. The potency of betulinic acid as an inhibitor of human platelet activation was evaluated, and its antiplatelet profile against in vitro platelet aggregation, induced by several platelet agonists (adenosine diphosphate, thrombin receptor activator peptide-14, and arachidonic acid), was explored. Flow cytometric analysis was performed to examine the effect of betulinic acid on P-selectin membrane expression and PAC-1 binding to activated platelets. Betulinic acid potently inhibits platelet aggregation and also reduced PAC-1 binding and the membrane expression of P-selectin. Principal component analysis was used to screen, on the chemical property space, for potential common pharmacophores of betulinic acid with approved antithrombotic drugs. A common pharmacophore was defined between the NMR-derived structure of betulinic acid and prostacyclin agonists (PGI2), and the importance of its carboxylate group in its antiplatelet activity was determined. The present results indicate that betulinic acid has potential use as an antithrombotic compound and suggest that the mechanism underlying the antiplatelet effects of betulinic acid is similar to that of the PGI2 receptor agonists, a hypothesis that deserves further investigation.