2α-Acetoxy-15-acetylartemisiifolin, a new Anti-trypanosomal Sesquiterpene Lactone from Mikania guaco

Mikania guaco Bonpl. methanol extract showed an interesting activity against Trypanosoma cruzi with an IC50 of 4 μg/mL. Bioassay-guided fractionation of the methanol extract resulted in the isolation of a new sesquiterpene lactone, 2α-acetoxy, 15-acetylartemisiifolin (1), which was shown to be active (IC50 = 25 μM) against the amastigote form of T. cruzi,. The chemical structure of 1 was elucidated using 2-D NMR techniques and mass spectrometry.

Brazilian Amazon Traditional Medicine and the Treatment of Difficult to Heal Leishmaniasis Wounds withCopaifera

The present study describes the use of the traditional speciesCopaiferafor treating wounds, such as ulcers scarring and antileishmanial wounds. It also relates phytochemical studies, evaluation of the leishmanicidal activity, and toxicity. The species ofCopaiferawith a higher incidence in the Amazon region areCopaifera officinalis,Copaifera reticulata,Copaifera multijugaHayne. The copaiba oil is used in the Amazon’s traditional medicine, especially as anti-inflammatory ingredient, in ulcers healing, and in scarring and for leishmaniasis. Chemical studies have shown that these oils contain diterpenes and sesquiterpenes. The copaiba oil and terpenes isolated have antiparasitic activity, more promising in the amastigote form ofL. amazonensis. This activity is probably related to changes in the cell membrane and mitochondria. The oil showed low cytotoxicity and genotoxicity. Furthermore, it may interfere with immune response to infection and also has a healing effect. In summary, the copaiba oil is promising as leishmanicidal agent.

Inhibition of Leishmania mexicana Growth by the Tuberculosis Drug SQ109

ABSTRACTWe report that the tuberculosis drug SQ109 [N-adamantan-2-yl-N′-((E)-3,7-dimethyl-octa-2,6-dienyl)-ethane-1,2-diamine] has potent activity against the intracellular amastigote form ofLeishmania mexicana(50% inhibitory concentration [IC50], ∼11 nM), with a good selectivity index (>500). It is also active against promastigotes (IC50, ∼500 nM) and acts as a protonophore uncoupler, in addition to disrupting Ca2+homeostasis by releasing organelle Ca2+into the cytoplasm, and as such, it is an interesting new leishmaniasis drug hit candidate.

Aurones: A Promising Heterocyclic Scaffold for the Development of Potent Antileishmanial Agents

A series of (Z)-2-benzylidenebenzofuran-3-(2H)-ones (aurones) bearing a variety of substituents on rings A and B were synthesized and evaluated for their antiparasitic activity against the intracellular amastigote form of Leishmania infantum and their cytotoxicity against human THP1-differentiated macrophages. In general, aurones bearing no substituents on ring A (compounds 4a–4f) exhibit higher toxicity than aurones with 4,6-dimethoxy substitution (compounds 4g–4l). Among the latter, two aurones possessing a 2′-methoxy or a 2′-methyl group (compounds 4i and 4j) exhibit potent antileishmanial activity (IC50=1.3±0.1 μM and IC50=1.6±0.2 μM, resp.), comparable to the activity of the reference drug Amphotericin B, whereas they present significantly lower cytotoxicity than Amphotericin B as deduced by the higher selectivity index.

Intracellular interactions of Leishmania mexicana with a cell line from Toxorhynchites amboinensis (77M-248) larvae

Leishmania is an intracellular parasite that lives in phagocytic vacuoles of macrophages . The promastigote form of the parasite is flagellated and interacts with macrophages through specific cell membrane receptors . Once inside phagocytic vacuoles, the parasite differentiates into the amastigote form which is small and aflagellated. Part of the life cycle of the parasite occurs in the lumen of the digestive tract of an insect, with a body temperature of 25-27 °C that promotes the preferential differentiation of the promastigote form. A cell line ( TRA-248 ) isolated from Toxorhynchites amboinensis has been adapted to grow at two different temperatures 24° and 34°C, and used in the study of dengue virus. This quality of TRA-248 cells is of relevance since they permit to analyze the behavior of leishmania in an insect cell at two distinct temperatures. In this study, TRA- 248 cells and promastigotes interacted in culture at 24° and 34°C, for 12, 24 and 48 hrs and determine if the parasites are phagocyted and able to differentiate into the amastigote form. Also, the activity of acid phosphatase was compared between TRA-248 cells and macrophages.

A heparin-binding activity on Leishmania amastigotes which mediates adhesion to cellular proteoglycans.

The intracellular amastigote form of leishmania is responsible for the cell-to-cell spread of leishmania infection in the mammalian host. In this report, we identify a high-affinity, heparin-binding activity on the surface of the amastigote form of leishmania. Amastigotes of Leishmania amazonensis bound approximately 120,000 molecules of heparin per cell, with a Kd of 8.8 x 10(-8) M. This heparin-binding activity mediates the adhesion of amastigotes to mammalian cells via heparan sulfate proteoglycans, which are expressed on the surface of mammalian cells. Amastigotes bound efficiently to a variety of adherent cells which express cell-surface proteoglycans. Unlike wild-type CHO cells, which bound amastigotes avidly, CHO cells with genetic deficiencies in heparan sulfate proteoglycan biosynthesis or cells treated with heparitinase failed to bind amastigotes even at high parasite-input dosages. Cells which express normal levels of undersulfated heparan bound amastigotes nearly as efficiently as did wild-type cells. The adhesion of amastigotes to wild-type nonmyeloid cells was almost completely inhibited by the addition of micromolar amounts of soluble heparin or heparan sulfate but not by the addition of other sulfated polysaccharides.l Binding of amastigotes to macrophages, however, was inhibited by only 60% after pretreatment of amastigotes with heparin, suggesting that macrophages have an additional mechanism for recognizing amastigotes. These results suggest that leishmania amastigotes express a high-affinity, heparin-binding activity on their surface which can interact with heparan sulfate proteoglycans on mammalian cells. This interaction may represent an important first step in the invasion of host cells by amastigotes.