Synthetic marine guanidines are effective antileishmanial compounds by altering the plasma membrane permeability

Neglected parasitic diseases as Leishmaniasis and Chagas disease affect 12 and 6 million people in tropical and subtropical countries, respectively. Co-infections with HIV and other parasitic diseases represent a major threat to Public Health. With a limited number of drugs in clinical use, the treatment is still deficient, including severe adverse effects [1]. Guanidine compounds has been widely found in natural products and especially in marine invertebrates. Marine sponges, in particular, are by far the most abundant source of all natural guanidine derivatives; the structural complexity of these compounds and their potent biological activities make these compounds a target of choice for studies in organic synthesis [2]. In this work, we studied the in vitro antileishmanial activity of a synthetic batzelladine alkaloid derivative and a ptilomycalin A derivative and their capability to alter the permeability of the plasma membrane of Leishmania. The in vitro assays demonstrated that Leishmania (L.) infantum was susceptible to the guanidine derivatives, EB-3 and GB-118, with IC50 values of 57 µg/mL and 33 µg/mL, respectively. The compounds also eliminated the intracellular forms of Leishmania with an IC50 value of 5 µg/mL and 2 µg/mL, respectively. The cytotoxicity of both compounds against NCTC cells resulted in CC50 values of 137 µg/mL and 45 µg/mL, demonstrating selectivity indexes of 27 and 22, respectively. Using the fluorescent probe SYTOX Green, it was possible to demonstrate that both compounds altered the plasma membrane permeability of Leishmania at the early time of incubation (< 60 min), but EB-3 affected the membrane to a higher extent, when compared to the positive control with Triton-X 100. These results indicate the potential of synthetic guanidine derivatives as novel drug prototypes for Leishmaniasis

Anti-parasitic Guanidine and Pyrimidine Alkaloids from the Marine Sponge Monanchora arbuscula

HPLC-UV-ELSD-MS-guided fractionation of the anti-parasitic extract obtained from the marine sponge Monanchora arbuscula, collected off the southeastern coast of Brazil, led to the isolation of a series of guanidine and pyrimidine alkaloids. The pyrimidines monalidine A (1) and arbusculidine A (7), as well as the guanidine alkaloids batzellamide A (8) and hemibatzelladines 9�11, represent new minor constituents that were identified by analysis of spectroscopic data. The total synthesis of monalidine A confirmed its structure. Arbusculidine A (7), related to the ptilocaulin/mirabilin/netamine family of tricyclic guanidine alkaloids, is the first in this family to possess a benzene ring. Batzellamide A (8) and hemibatzelladines 9�11 represent new carbon skeletons that are related to the batzelladines. Evaluation of the anti-parasitic activity of the major known metabolites, batzelladines D (12), F (13), L (14), and nor-L (15), as well as of synthetic monalidine A (1), against Trypanosoma cruzi and Leishmania infantum is also reported, along with a detailed investigation of parasite cell-death pathways promoted by batzelladine L (14) and norbatzelladine L (15)

Bioactivity And Chemical Composition Of The Essential Oil From The Leaves Of Guatteria Australis A.st.-hil

Essential oil from the leaves of Guatteria australis was obtained by hydrodistillation, analyzed by Gas Chromatography coupled to Mass Spectromery (GC–MS) and their antiproliferative, antileishmanial, antibacterial, antifungal and antioxidant activities were also evaluated. Twenty-three compounds were identified among which germacrene B (50.66%), germacrene D (22.22%) and (E)-caryophyllene (8.99%) were the main compounds. The highest antiproliferative activity was observed against NCI-ADR/RES (TGI = 31.08 μg/ml) and HT-29 (TGI = 32.81 μg/ml) cell lines. It also showed good antileishmanial activity against Leishmania infantum (IC50 = 30.71 μg/ml). On the other hand, the oil exhibited a small effect against Staphylococcus aureus ATCC 6538, S. aureus ATCC 14458 and Escherichia coli ATCC 10799 (MIC = 250 μg/ml), as well as small antioxidant activity (457 μmol TE/g) assessed through ORACFL assay. These results represent the first report regarding chemical composition and bioactivity of G. australis essential oil