In silico study of structural and geometrical requirements of natural sesquiterpene lactones with trypanocidal activity.

Chagas' disease, caused by the intracellular protozoan Trypanosoma cruzi, is one of the most serious health problems throughout South America. Despite the progress that has been made in the study of its biochemistry and physiology, more efficient chemotherapies to control this parasitic infection are still lacking. In this paper we report the trypanocidal and cytotoxic activities of a series of sesquiterpene lactones, isolated from Asteraceae medicinal plants. The significant trypanocidal activity and high selectivity indexes found for many of the compounds evaluated, prompted us to undertake a quantitative structure-activity relationship study. A model using 3D molecular descriptors allowed us to set up a high correlation of the observed activity and the atomic spatial arrangement of these sesquiterpene lactones closely related to steric parameters.

Trypanocidal Activity of Smallanthus sonchifolius: Identification of Active Sesquiterpene Lactones by Bioassay-Guided Fractionation.

In order to find novel plant-derived biologically active compounds against Trypanosoma cruzi, we isolated, from the organic extract of Smallanthus sonchifolius, the sesquiterpene lactones enhydrin (1), uvedalin (2), and polymatin B (3) by bioassay-guided fractionation technique. These compounds showed a significant trypanocidal activity against the epimastigote forms of the parasite with IC50 values of 0.84 µ M (1), 1.09 µ M (2), and 4.90 µ M (3). After a 24 h treatment with 10 µ g/mL of enhydrin or uvedalin, parasites were not able to recover their replication rate. Compounds 1 and 2 showed IC50 values of 33.4 µ M and 25.0 µ M against T. cruzi trypomastigotes, while polymatin B was not active. When the three compounds were tested against the intracellular forms of T. cruzi, they were able to inhibit the amastigote replication with IC50 of 5.17 µ M, 3.34 µ M, and 9.02 µ M for 1, 2, and 3, respectively. The cytotoxicity of the compounds was evaluated in Vero cells obtaining CC50 values of 46.5 µ M (1), 46.8 µ M (2), and 147.3 µ M (3) and the selectivity index calculated. According to these results, enhydrin and uvedalin might have potentials as agents against Chagas disease and could serve as lead molecules to develop new drugs.

In Vitro Antiplasmodial Activity of Sesquiterpene Lactones from Ambrosia tenuifolia.

The in vitro antiplasmodial activity of Ambrosia tenuifolia organic extract and its isolated sesquiterpene lactones, psilostachyin and peruvin, has been evaluated against Plasmodium falciparum F32 and W2 strains. The cytotoxicity of both compounds was determined on lymphoid cells, and their corresponding selectivity indexes (SIs) were calculated. Peruvin was the most active compound on F32 strain of P. falciparum with a 50% inhibitory concentration value (IC(50)) of 0.3 µg/mL (1.1 µM) whereas psilostachyin showed activity on both strains (IC(50) = 0.6 (2.1 µM) and 1.8 µg/mL (6.4 µM)). Fifty percent cytotoxic concentration (CC(50)) values (48 h) were 6.8 µg/mL (24.3 µM) and 10.0 µg/mL (37.9 µM) for psilostachyin and peruvin, respectively.

In vitro evaluation of trypanocidal activity in plants used in Argentine traditional medicine.

Thirty-two organic and aqueous extracts, belonging to 12 Argentine medicinal plants were tested for their in vitro trypanocidal activity on epimastigote forms of Trypanosoma cruzi. Among the selected species, the organic extracts of Ambrosia scabra, Ambrosia tenuifolia, Baccharis spicata, Eupatorium buniifolium, Lippia integrifolia, Mulinum spinosum and Satureja parvifolia, and the aqueous extracts of E. buniifolium, L. integrifolia, M. spinosum and S. parvifolia showed trypanocidal activity with a percentage of growth inhibition higher than 70% at a concentration of 100 microg/ml.

Antinociceptive activity of Eupatorium buniifolium aqueous extract.

The antinociceptive properties of the aqueous extract of Eupatorium buniifolium aerial parts were investigated in chemical and thermal models of nociception in mice. Oral doses of 250 and 500 mg/kg produced an inhibition of 42.3% and 73.9%, respectively, of the abdominal writhes induced by acetic acid in mice. This antinociceptive effect was not reversed by pretreatment with naloxone. In the formalin test, the administration of 500 and 1000 mg/kg p.o. had no effects in the first phase (0-5 min) but produced a dose-dependent analgesic effect on the second phase (15-30 min) with inhibitions of the licking time of 38.9% and 57.3%, respectively. In the hot plate test, no effect was seen at the dose of 500 mg/kg p.o.

In vitro antiplasmodial activity of extracts of Argentinian plants.

Fifteen extracts from nine selected Argentine medicinal plants were tested for their antiplasmodial activity in vitro by assessing their ability to inhibit the uptake of [3H]-hypoxanthine into the Plasmodium falciparum K1 pyrimethamine/chloroquine resistant strain. The methanol extract of Satureja parvifolia showed good antiplasmodial activity (IC(50) 3 microg/ml). Inhibition of the growth of P. falciparum was also observed with aqueous extracts of Buddleja globosa and S. parvifolia.

Phenolic compounds with anti-inflammatory activity from Eupatorium buniifolium.

Anti-inflammatory activity was detected in the CH(2)Cl(2) extract of the aerial parts of Eupatorium buniifolium using the TPA-mouse ear model. Three compounds isolated from this extract, by bioassay-guided fractionation, significantly inhibited the inflammatory response. The compounds were identified as 5,7,5'-trihydroxy-3,6,2',4'-tetramethoxyflavone (1), scopoletin (2) and centaureidin (3) which inhibited the edema by 67.3 %, 59.8 % and 49.7 %, respectively, at a dose of 1 mg/ear.

Transverse instability of magnetized electron holes

We study a transverse instability of the nonlinear equilibria known as electron phase-space holes in the presence of a magnetic field. The instability is intrinsically two dimensional and is determined by the dynamics of the trapped electrons. It depends on hole amplitudes, ambient magnetic fields, and the perpendicular velocity spread. The long-standing hole stability problem in multiple dimensions can be characterized by the gyro-to-bounce frequency ratio. A low ratio associated with a small perpendicular velocity spread results in a disintegration of the positive potential spikes.

Argentine plant extracts active against polymerase and ribonuclease H activities of HIV-1 reverse transcriptase.

Lipophilic and hydrophilic extracts of four Argentine plants (Gamochaeta simplicaulis Cabr. 1, Achyrocline flaccida Wein. D. C. 2, Eupatorium buniifolium H. et A. 3, and Phyllanthus sellowianus Muell. Arg. 4) were examined in vitro for their ability to inhibit the polymerase and ribonuclease H (RNase H) activities of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) (wild and Y181C mutant types). The active extracts were also examined as inhibitors of viral replication in HLT4LacZ-1IIIB cell cultures, evaluating their cytotoxicity in parallel. Infusions 2I and 4I, among the crude extracts, showed the highest activity. These extracts were refractioned into four fractions; 2I4 and 4I4 were active as inhibitors of DNA-polymerase (wild and Y181C types) and RNase H activities. These fractions were potent as inhibitors of viral replication and were not cytotoxic. Refractionation of 2I4 yielded five new fractions, two of which, 2I4-4 and 2I4-5, showed notable activity. Refractionation of 4I4 yielded for new fractions; of these, 4I4-3 and 4I4-4 were active. The marked biological activity found in the infusion of A. flaccida and P. sellowianus makes them sufficiently attractive to be considered in the combined chemotherapy of the disease.

Search for antiinflammatory activity in Argentine Medicinal Plants.

Extracts of different polarity from four Argentine medicinal plants used in folk medicine as antiinflammatory remedies were tested for bioactivity using carrageenan-induced paw edema in rats and TPA-induced ear edema in mice. A dichloromethane extract from Pluchea sagittalis showed good antiinflammatory activity in both tests. Flavonoids present in this extract may be responsible for the activity. Ipomoea fistulosa dichloromethane extract showed significant activity in the ear edema test while a dichloromethane extract from Eupatorium inulaefolium and aqueous extract of Polygonum punctatum exhibited antiinflammatory activity in the carrageenan-induced edema test.