A fluorinated phenylbenzothiazole arrest the Trypanosoma cruzi cell cycle and diminishes the mammalian host-cell infection.

A fluorinated phenylbenzothiazole arrest the Trypanosoma cruzi cell cycle and diminishes the mammalian host-cell infection. Antimicrob Agents Chemother. 2019 Nov 11;: Authors: Cuevas-Hernández RI, Girard RMBM, Martínez-Cerón S, Santos da Silva M, Elias MC, Crispim M, Trujillo-Ferrara JG, Silber AM Abstract Chagas disease (CD) is a human infection caused by Trypanosoma cruzi CD was traditionally endemic to the Americas, however, due to migration it has spread to non-endemic countries. The current chemotherapy to treat CD induce several side effects and its effectiveness in the chronic phase of the disease is controversial. In this contribution, substituted phenylbenzothiazole derivatives were synthesized and biologically evaluated as trypanocidal agents against Trypanosoma cruzi The trypanocidal activities of the most promising compounds were determined through systematic in vitro screening and their mode of action as well. The physicochemical-structural characteristics responsible for the trypanocidal effects were identified, and their possible therapeutic application in Chagas disease is discussed. Our results show that the fluorinated compound, 2-methoxy-4-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl] phenol (BT10) has the ability to inhibit the proliferation of epimastigotes (IC50(Epi) = 23.1 ± 1.75 μM) and intracellular forms trypomastigote (IC50(Tryp) = 8.5 ± 2.9 μM) and diminishes the infection index by more t...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research

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by Higo Fernando Santos Souza, Sandra Carla Rocha, Fl ávia Silva Damasceno, Ludmila Nakamura Rapado, Elisabeth Mieko Furusho Pral, Claudio Romero Farias Marinho, Ariel Mariano Silber Chagas disease, caused byTrypanosoma cruzi, is a neglected tropical disease that affects 5 –6 million people in endemic areas of the Americas. Presently, chemotherapy relies on two compounds that were proposed as trypanocidal drugs four decades ago: nifurtimox and benznidazole. Both drugs are able to eliminate parasitemia and to avoid seroconversion in infected people when used in the a cute phase; however, their use in the chron...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
an AG Abstract Chagas disease has become a global health problem due to migration of infected people out of Latin America to non-endemic countries. For more than 40 years, only the nitroimidazole compounds Benznidazole and Nifurtimox, have been used for specific treatment of Trypanosoma cruzi infection with disappointing results, specially due to the long duration of treatment and adverse events in the chronic phase. In the last years, ergosterol inhibitors have been also proposed for specific treatment. Different randomized clinical trials were performed for evaluating their treatment efficacy and safety. One of ...
Source: Acta Tropica - Category: Infectious Diseases Authors: Tags: Acta Trop Source Type: research
AbstractChagas disease is endemic in Latin America and increasingly found in non-endemic countries. Its treatment is limited due to the variable efficacy and several side effects of benznidazole. Photodynamic antimicrobial chemotherapy (PACT) may be an attractive approach for treating Chagas disease. Here, the trypanocidal activity of PACT was investigated in vitro using phenothiazine derivatives. The cytotoxicity of both, methylene blue (MB) and toluidine blue (TBO), was determined on macrophages cultures using AlamarBlue method. The trypanocidal activity of the two photosensitizers was initially evaluated by determining ...
Source: Lasers in Medical Science - Category: Laser Surgery Source Type: research
Imidazole derivatives as promising agents for the treatment of Chagas disease†. Antimicrob Agents Chemother. 2019 Jan 22;: Authors: de Araújo JS, Garcia-Rubia A, Sebastian-Perez V, Kalejaiye TD, Bernardino da Silva P, Fonseca-Berzal CR, Maes L, De Koning HP, Soeiro MNC, Gil C Abstract More than 100 years later after being firstly described, Chagas disease remains endemic in 21 Latin American countries and has spread to other continents. Indeed, this disease, caused by the protozoan parasite Trypanosoma cruzi, is no longer just a problem for the American continent but has become a global ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
This article describes the first micro-sampling method for measuring BNZ levels in DBS that has the potential to facilitate broad implementation of PK in clinical trials involving adult and paediatric patients in remote endemic areas and help to address existing knowledge gaps in the treatment in CD. PMID: 30275095 [PubMed - as supplied by publisher]
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
In this study, we were able to achieve a 4-fold reduction in the amount of benznidazole required to significantly reduce blood and tissue parasite burdens by combining the low-dose benznidazole with a recombinant vaccine candidate, Tc24 C4, formulated with a synthetic Toll-like 4 receptor agonist, E6020, in a squalene oil-in-water emulsion. Additionally, vaccination induced a robust parasite-specific balanced TH1/TH2 immune response. We concluded that vaccine-linked chemotherapy is a feasible option for advancement to clinical use for improving the tolerability and efficacy of benznidazole.
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Microbial Immunity and Vaccines Source Type: research
CONCLUSIONS: Our results do not support a clinical association between chronic Chagas disease and systemic autoimmune diseases. However, prospective studies in areas endemic for Chagas disease should better assess the prevalence of systemic autoimmune diseases and thus a possible relationship with this infection. PMID: 29412344 [PubMed - in process]
Source: Memorias do Instituto Oswaldo Cruz - Category: Infectious Diseases Authors: Tags: Mem Inst Oswaldo Cruz Source Type: research
Publication date: Available online 1 June 2017 Source:Pharmacology & Therapeutics Author(s): Leonardo G. Ferreira, Adriano D. Andricopulo Chagas disease and human African trypanosomiasis are endemic conditions in Latin America and Africa, respectively, for which no effective and safe therapy is available. Efforts in drug discovery have focused on several enzymes from these protozoans, among which cysteine proteases have been validated as molecular targets for pharmacological intervention. These enzymes are expressed during the entire life cycle of trypanosomatid parasites and are essential to many biological processes...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research
(Bentham Science Publishers) Chagas disease is a parasitic infection typically spread by triatomine vectors, affecting millions of people all over Latin America. Existing chemotherapy is centered on benznidazole and nifurtimox, providing unsatisfactory results and substantial side effects. The transmission of the disease by people migration has determined the emergence as a public health problem elsewhere in non-endemic countries of the word. So, the finding of novel ways to challenge this neglected disease is a main priority.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Conclusion/SignificanceOur results point to different modes of action for N1, N2 and N3, which indicate a great variety of metabolic pathways involved and allow for novel perspectives on the development of trypanocidal agents.
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
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