Chagas disease (CD) caused by the protozoan affects more than six million people worldwide. Treatment is restricted to benznidazole (Bz) and nifurtimox (Nf) that display low activity in the later chronic stage besides triggering toxic events that result in treatment abandonment. Therefore, new therapeutic options are necessary.
View Article and Find Full Text PDFActa Trop
June 2023
Atorvastatin (AVA) is a third-generation statin with several pleiotropic effects, considered the last synthetic pharmaceutical blockbuster. Recently, our group described the effects of AVA on DNA damage prevention and against Trypanosoma cruzi infection. In this study, our aim was to evaluate the efficacy, safety, and in silico pharmacokinetic profile of four hybrids of aminoquinolines with AVA 4a-d against T.
View Article and Find Full Text PDFChagas disease (CD) affects more than 6 million people worldwide. The available treatment is far from ideal, creating a demand for new alternative therapies. Botanical diversity provides a wide range of novel potential therapeutic scaffolds.
View Article and Find Full Text PDFAzoles such as posaconazole (Posa) are highly potent against . However, when tested in chronic Chagas disease patients, a high rate of relapse after Posa treatment was observed. It appears that inhibition of cytochrome CYP51, the target of azoles, does not deliver sterile cure in monotherapy.
View Article and Find Full Text PDFThe phosphodiesterase inhibitor tetrahydrophthalazinone NPD-008 was explored by phenotypic screening, target validation, and ultrastructural approaches against NPD-008 displayed activity against different forms and strains of (50% effective concentration [EC], 6.6 to 39.5 μM).
View Article and Find Full Text PDFIn previous studies, we have identified several families of 5-nitroindazole derivatives as promising antichagasic prototypes. Among them, 1-(2-aminoethyl)-2-benzyl-5-nitro-1,2-dihydro-3H-indazol-3-one, (hydrochloride) and 1-(2-acetoxyethyl)-2-benzyl-5-nitro-1,2-dihydro-3H-indazol-3-one (compounds 16 and 24, respectively) have recently shown outstanding activity in vitro over the drug-sensitive Trypanosoma cruzi CL strain (DTU TcVI). Here, we explored the activity of these derivatives against the moderately drug-resistant Y strain (DTU TcII), in vitro and in vivo.
View Article and Find Full Text PDFBackground: Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, needs urgent alternative therapeutic options as the treatments currently available display severe limitations, mainly related to efficacy and toxicity.
Objectives: As phosphodiesterases (PDEs) have been claimed as novel targets against T. cruzi, our aim was to evaluate the biological aspects of 12 new phthalazinone PDE inhibitors against different T.
Chagas disease is a neglected pathology responsible for about 12,000 deaths every year across Latin America. Although six million people are infected by the Trypanosoma cruzi, current therapeutic options are limited, highlighting the need for new drugs. Here we report the preliminary structure activity relationships of a small library of 17 novel pyridyl sulfonamide derivatives.
View Article and Find Full Text PDFChem Biol Drug Des
September 2018
Chagas disease has spread throughout the world mainly because of the migration of infected individuals. In Brazil, only benznidazole (Bnz) is used; however, it is toxic and not active in the chronic phase, and cases of resistance are described. This work aimed at the synthesis and the trypanocidal evaluation in vitro and in vivo of six new Bnz analogues (3-8).
View Article and Find Full Text PDFEur J Med Chem
April 2018
American trypanosomiasis or Chagas disease (CD) is a vector borne pathology caused by the parasite Trypanosoma cruzi (T. cruzi), which remains a serious global health problem. The current available treatment for CD is limited to two nitroderivatives with limited efficacy and several side effects.
View Article and Find Full Text PDFAntimicrob Agents Chemother
February 2018
Five bis-arylimidamides were assayed as anti- agents by , , and approaches. None were considered to be pan-assay interference compounds. They had a favorable pharmacokinetic landscape and were active against trypomastigotes and intracellular forms, and in combination with benznidazole, they gave no interaction.
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