amphotericin-b and Trypanosomiasis

2-Amino-benzo[ d]thiazole was identified as a new scaffold for the development of improved pteridine reductase-1 (PTR1) inhibitors and anti-trypanosomatidic agents. Molecular docking and crystallography guided the design and synthesis of 42 new benzothiazoles. The compounds were assessed for Trypanosoma brucei and Leishmania major PTR1 inhibition and in vitro activity against T. brucei and amastigote Leishmania infantum. We identified several 2-amino-benzo[ d]thiazoles with improved enzymatic activity ( TbPTR1 IC

Topics: Animals; Antiprotozoal Agents; Benzothiazoles; Binding Sites; Catalytic Domain; Crystallography, X-Ray; Drug Design; Enzyme Inhibitors; Half-Life; Leishmania major; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Oxidoreductases; Protozoan Proteins; Structure-Activity Relationship; Trypanosoma brucei brucei; Trypanosomiasis

Human trypansomiasis due to infection by animal trypanosomes is rarely reported from India.. We describe clinical presentation of a 2-month-old boyfrom a rat infested house in rural Gujarat who was diagnosed to be havinginfection with the rodent parasite Trypanosoma lewisi.. The fever and parasitemia resolved on treatment with liposomal amphotericin B, Ceftriaxone and Amikacin, and there was no recurrence of parasitemia over a 2 month follow-up.. The case highlights the need for increased awareness and heightened surveillance for this rare zoonotic infection.

Topics: Amphotericin B; Animals; Antiprotozoal Agents; Fever of Unknown Origin; Humans; India; Infant; Parasitemia; Rats; Trypanosoma lewisi; Trypanosomiasis; Zoonoses

In our search for new protein farnesyltransferase inhibitors with improved antiparasitic activities, we modified our previously developed 3-arylthiophene series of inhibitors by replacing the thioisopropyl group by different substituted imidazolylmethanamino moieties. Twenty four new derivatives were synthesized and evaluated against human and parasite farnesyltransferases, and their anti-parasitic activity was determined against Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi, and Leishmania donovani. Introduction of a N-p-substituted-benzylimidazole led to significantly increase the inhibition of parasite proliferation in the submicromolar range. The structure of the best inhibitors was parasite dependent. Three compounds possess IC50 values at the same range as the reference miltefosine against L. donovani proliferation and other new derivatives display high level of anti-trypanosomal activity against T. cruzi, higher or in the same order of magnitude as the reference compounds benznidazole and nifurtimox.

Topics: Alkyl and Aryl Transferases; Animals; Antiparasitic Agents; Cell Line; Enzyme Inhibitors; Humans; Imidazoles; Leishmania donovani; Leishmaniasis, Visceral; Malaria, Falciparum; Mice; Parasitic Sensitivity Tests; Plasmodium falciparum; Trypanosoma; Trypanosoma brucei brucei; Trypanosoma cruzi; Trypanosomiasis

Treatment of diseases such as African sleeping sickness and leishmaniasis often depends on relatively expensive or toxic drugs, and resistance to current chemotherapeutics is an issue in treating these diseases and malaria. In this study, a new semi-synthetic berberine analogue, 5,6-didehydro-8,8-diethyl-13-oxodihydroberberine chloride (1), showed nanomolar level potency against in vitro models of leishmaniasis, malaria, and trypanosomiasis as well as activity in an in vivo visceral leishmaniasis model. Since the synthetic starting material, berberine hemisulfate, is inexpensive, 8,8-dialkyl-substituted analogues of berberine may lead to a new class of affordable antiprotozoal compounds.

Topics: Animals; Antiprotozoal Agents; Berberine; Chlorocebus aethiops; Disease Models, Animal; Inhibitory Concentration 50; Leishmania; Leishmaniasis; Malaria; Mice; Models, Molecular; Parasites; Plasmodium falciparum; Protozoan Infections; Trypanosoma brucei brucei; Trypanosomiasis; Vero Cells

Trypanosomes were observed in the peripheral blood smear of a 37-day-old Indian infant admitted off feeds, with fever and convulsions. Trypanosoma (Herpetosoma) lewisi was identified in the blood. The species identification was confirmed by morphometry, polymerase chain reaction, and sequencing. Human infection with this organism is rare. Only seven cases of this infection have been reported previously in humans. The cases reported are reviewed to develop a composite picture of this disease.

Topics: Amphotericin B; Anti-Bacterial Agents; Antiprotozoal Agents; Ceftriaxone; Humans; Infant; Male; Pentamidine; Trypanosoma lewisi; Trypanosomiasis

Topics: Amphotericin B; Animals; Cell Line; Dose-Response Relationship, Drug; Lung; Male; Mice; Trypanosoma cruzi; Trypanosomiasis

Topics: Amphotericin B; Antifungal Agents; Chagas Disease; Fungicides, Industrial; Trypanosoma cruzi; Trypanosomiasis; United States

Topics: Amphotericin B; Antifungal Agents; Chagas Disease; Fungicides, Industrial; Hispanic or Latino; Humans; Trypanosomiasis; United States