Search results for "Antiprotozoal"
showing 10 items of 65 documents
Comparing the Antileishmanial Activity of Gold(I) and Gold(III) Compounds in L. amazonensis and L. braziliensis in Vitro
2020
Abstract Abstract: A series of mononuclear coordination or organometallic AuI/AuIII complexes (1–9) have been comparatively studied in vitro for their antileishmanial activity against promastigotes and amastigotes, the clinically relevant parasite form, of Leishmania amazonensis and Leishmania braziliensis. One of the cationic AuI bis‐N‐heterocyclic carbenes (3) has low EC50 values (ca. 4 μM) in promastigotes cells and no toxicity in host macrophages. Together with two other AuIII complexes (6 and 7), the compound is also extremely effective in intracellular amastigotes from L. amazonensis. Initial mechanistic studies include an evaluation of the gold complexes′ effect on L. amazonensis’ pl…
Molecular Search of New Active Drugs AgainstToxoplasma Gondii
1999
Molecular connectivity has been applied to the search of new compounds with activity against the protozoan Toxoplasma gondii, using a stepwise linear discriminant analysis (SLDA) which is able to classify a compound according its activity either as active or as inactive. Among the selected compounds, andrographolide and dibenzotiophene sulfone stand out, both with IC50 values lower than 1 microgram/ml, which are comparable to these of drugs such as sulfamethoxazole, pyrimethamine and trimethoprim, with IC50 values equal to 1.1, 0.04 and 2.31 micrograms/ml, respectively. These results confirm the usefulness of our topological approach for the selection and design of new-lead drugs active aga…
Development of Novel Benzodiazepine-Based Peptidomimetics as Inhibitors of Rhodesain from Trypanosoma brucei rhodesiense.
2020
Starting from the reversible rhodesain inhibitors 1 a-c, which have Ki values towards the target protease in the low-micromolar range, we have designed a series of peptidomimetics, 2 a-g, that contain a benzodiazepine scaffold as a β-turn mimetic; they are characterized by a specific peptide sequence for the inhibition of rhodesain. Considering that irreversible inhibition is strongly desirable in the case of a parasitic target, a vinyl ester moiety acting as Michael-acceptor was introduced as the warhead; this portion was functionalized in order to evaluate the size of corresponding enzyme pocket that could accommodate this substituent. With this investigation, we identified an irreversibl…
In vitro and in vivo antileishmanial and trypanocidal studies of new N-benzene- and N-naphthalenesulfonamide derivatives.
2013
We report in vivo and in vitro antileishmanial and trypanocidal activities of a new series of N-substituted benzene and naphthalenesulfonamides 1-15. Compounds 1-15 were screened in vitro against Leishmania infantum , Leishmania braziliensis , Leishmania guyanensis , Leishmania amazonensis , and Trypanosoma cruzi . Sulfonamides 6e, 10b, and 10d displayed remarkable activity and selectivity toward T. cruzi epimastigotes and amastigotes. 6e showed significant trypanocidal activity on parasitemia in a murine model of acute Chagas disease. Moreover, 6e, 8c, 9c, 12c, and 14d displayed interesting IC50 values against Leishmania spp promastigotes as well as L. amazonensis and L. infantum amastigot…
New ligand-based approach for the discovery of antitrypanosomal compounds.
2005
The antitrypanosomal activity of 10 already synthesized compounds was in silico predicted as well as in vitro and in vivo explored against Trypanosoma cruzi. For the computational study, an approach based on non-stochastic linear fingerprints to the identification of potential antichagasic compounds is introduced. Molecular structures of 66 organic compounds, 28 with antitrypanosomal activity and 38 having other clinical uses, were parameterized by means of the TOMOCOMD-CARDD software. A linear classification function was derived allowing the discrimination between active and inactive compounds with a confidence of 95%. As predicted, seven compounds showed antitrypanosomal activity (%AE > 7…
Inhibitor-Induced Dimerization of an Essential Oxidoreductase from African Trypanosomes
2018
Trypanosomal and leishmanial infections claim tens of thousands of lives each year. The metabolism of these unicellular eukaryotic parasites differs from the human host and their enzymes thus constitute promising drug targets. Tryparedoxin (Tpx) from Trypanosoma brucei is the essential oxidoreductase in the parasite's hydroperoxide-clearance cascade. In vitro and in vivo functional assays show that a small, selective inhibitor efficiently inhibits Tpx. With X-ray crystallography, SAXS, analytical SEC, SEC-MALS, MD simulations, ITC, and NMR spectroscopy, we show how covalent binding of this monofunctional inhibitor leads to Tpx dimerization. Intra- and intermolecular inhibitor-inhibitor, pro…
Synthesis and biological evaluation of papain-family cathepsin L-like cysteine protease inhibitors containing a 1,4-benzodiazepine scaffold as antipr…
2014
Novel papain-family cathepsin L-like cysteine protease inhibitors endowed with antitrypanosomal and antimalarial activity were developed, through an optimization study of previously developed inhibitors. In the present work, we studied the structure-activity relationships of these derivatives, with the aim to develop new analogues with a simplified and more synthetically accessible structure and with improved antiparasitic activity. The structure of the model compounds was significantly simplified by modifying or even eliminating the side chain appended at the C3 atom of the benzodiazepine scaffold. In addition, a simple methylene spacer of appropriate length was inserted between the benzod…
Leishmaniasis in travelers: A literature review.
2014
Leishmaniasis is a vector-borne protozoan infection whose clinical spectrum ranges from asymptomatic infection to fatal visceral leishmaniasis. Over the last decades, an increase in imported leishmaniasis cases in developed, non-endemic countries, have been pointed-out from a review of the international literature. Among the possible causes are increasing international tourism, influx of immigrants from endemic regions and military operations. The main area for the acquisition of cutaneous leishmaniasis, especially for adventure travelers on long-term trips in highly-endemic forested areas, is represented from South America, whereas popular Mediterranean destinations are emerging as the mai…
Entzündungshemmende wirkstoffe. XI. Ringschlußreaktion an 5-phenyl-2-thiobiuret
1988
Die Umsetzung von 5-Phenyl-2-thiobiuret (1) mil α-Chlorcarbonylverbindungen 2 fuhrt zu den N-Phenyl-N′-(2-thiazolyl)harnstoffen (3). Unter den neuen Verbindungen finden sich besonders die entzundungshemmende, anthelminthische und trichomonazide Wirksamkeit stark ausgepragt. The reaction of 5-phenyl-2-thiobiuret (1) with α-chlorocarbonyl compounds 2 leads to the structure type of N-phenyl-N1-(thiazolyl)urea (3). The new compounds exhibit particularly antiinflammatory, anthelminthic, and trichomonacidal activity.