Trypanosoma cruzi Dihydrolipoamide Dehydrogenase as Target for Phenothiazine Cationic Radicals. Effect of Antioxidants

Gutiérrez-Correa, José

doi:10.2174/138945006778226615

Cited by 13 publications

(5 citation statements)

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“…5 Gutierrez-Correa studied the antioxidant efficiency of various PTZ derivatives for Trypanosoma cruzi LADH (T. cruzi LADH) inactivation. 10 The inactivation of T. cruzi LADH depends on the rate of production of PTZ radical cations. The production of PTZ radical cations was correlated with the electron donor ability of the substrates and of the alkylated PTZ.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Lucarini et al described higher oxidation potentials for N-methylated PTZ derivatives in comparison with nonalkylated PTZ derivatives . Gutierrez-Correa studied the antioxidant efficiency of various PTZ derivatives for Trypanosoma cruzi LADH ( T. cruzi LADH) inactivation . The inactivation of T. cruzi LADH depends on the rate of production of PTZ radical cations.…”

Section: Introductionmentioning

confidence: 99%

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Efficient Polymerization Inhibition Systems for Acrylic Acid Distillation: New Liquid-Phase Inhibitors

Mosnáček

Nicolaÿ

Kar

et al. 2012

Ind. Eng. Chem. Res.

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Phenothiazine and other compounds with similar structures, namely, phenoxazine, promazine, promazine hydrochloride, N,N′-dimethylphenazine, carbazole, N-ethylcarbazole, N-benzylphenothiazine, and N-(1-phenylethyl)phenothiazine were tested as liquid-phase inhibitors for acrylic acid. N-Alkylated phenothiazine (PTZ) derivatives, such as Nbenzylphenothiazine and especially N-(1-phenylethyl)phenothiazine, showed improved efficiency for liquid-phase inhibition, in comparison with PTZ. It was also shown that N-alkylated PTZ derivatives could be used in combination with nitroso compounds that can be employed as vapor-phase inhibitors. The combination of N-(1-phenylethyl)phenothiazine and nitrosobenzene showed superior liquid-phase-inhibition efficiency, with time to gelation of >122 h, in comparison with 64 h obtained with PTZ alone. The structure of liquid-phase inhibitors had no influence on the extent of Michael addition reactions during heating of acrylic acid.

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Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficient Polymerization Inhibition Systems for Acrylic Acid Distillation: New Liquid-Phase Inhibitors

Mosnáček

Nicolaÿ

Kar

et al. 2012

Ind. Eng. Chem. Res.

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“…Thioridazine improves cardiac function and survival time in acute and chronic murine models of Chagas’ disease [ 28 ]. Moreover, phenothiazine derivatives also inhibit two major T. cruzi enzymes: trypanothione reductase and dihydrolipoamide dehydrogenase [ 50 , 51 ]. Due to the close taxonomic relationship between Leishmania spp.…”

Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Antileishmanial Activity of Thioridazine

Sifontes-Rodríguez,

Mollineda-Diogo,

Monzote-Fidalgo

et al. 2023

Acta Parasit.

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Introduction Leishmaniasis is a neglected disease with high prevalence and incidence in tropical and subtropical areas. Existing drugs are limited due to cost, toxicity, declining efficacy and unavailability in endemic places. Drug repurposing has established as an efficient way for the discovery of drugs for a variety of diseases. Purpose The objective of the present work was testing the antileishmanial activity of thioridazine, an antipsychotic agent with demonstrated effect against other intracellular pathogens. Methods The cytotoxicity for mouse peritoneal macrophages as well as the activity against Leishmania amazonensis, Leishmania mexicana and Leishmania major promastigotes and intracellular amastigotes, as well as in a mouse model of cutaneous leishmaniasis, were assessed. Results Thioridazine inhibited the in vitro proliferation of promastigotes (50% inhibitory concentration—IC50—values in the range of 0.73 µM to 3.8 µM against L. amazonensis, L. mexicana and L. major) and intracellular amastigotes (IC50 values of 1.27 µM to 4.4 µM for the same species). In contrast, in mouse peritoneal macrophages, the 50% cytotoxic concentration was 24.0 ± 1.89 µM. Thioridazine inhibited the growth of cutaneous lesions and reduced the number of parasites in the infected tissue of mice. The dose of thioridazine that inhibited lesion development by 50% compared to controls was 23.3 ± 3.1 mg/kg and in terms of parasite load, it was 11.1 ± 0.97 mg/kg. Conclusions Thioridazine was effective against the promastigote and intracellular amastigote stages of three Leishmania species and in a mouse model of cutaneous leishmaniasis, supporting the potential repurposing of this drug as an antileishmanial agent.

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“…Since the active site of CYP51 contains a heme iron, a radical burst could be triggered by its interaction with ergosterol peroxide, which would act as an enzymatic inhibitor generating long-lived radicals or carbonyl moieties to name a few examples [56]. The function of these radicals as enzyme inhibitors, or as generators of secondary free radicals and metabolite inactivators, could enhance their chemotherapeutic effects against Tc [24,57]. With these two mechanisms taking place separately or in conjunction, Tc might enter apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Insights into Ergosterol Peroxide’s Trypanocidal Activity

et al. 2019

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Trypanosoma cruzi, which causes Chagas disease, is a significant health threat in many countries and affects millions of people. Given the magnitude of this disease, a broader understanding of trypanocidal mechanisms is needed to prevent and treat infection. Natural endoperoxides, such as ergosterol peroxide, have been shown to be toxic to parasites without causing harm to human cells or tissues. Although prior studies have demonstrated the trypanocidal activity of ergosterol peroxide, the cellular and molecular mechanisms remain unknown. The results of this study indicate that a free-radical reaction occurs in T. cruzi following ergosterol peroxide exposure, leading to cell death. Using a combination of biochemical, microscopic and in silico experimental approaches, we have identified, for the first time, the cellular and molecular cytotoxic mechanism of an ergosterol peroxide obtained from Pleurotus ostreatus (Jacq) P. Kumm. f. sp. Florida.

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Trypanosoma cruzi Dihydrolipoamide Dehydrogenase as Target for Phenothiazine Cationic Radicals. Effect of Antioxidants

Cited by 13 publications

References 0 publications

Efficient Polymerization Inhibition Systems for Acrylic Acid Distillation: New Liquid-Phase Inhibitors

Efficient Polymerization Inhibition Systems for Acrylic Acid Distillation: New Liquid-Phase Inhibitors

In Vitro and In Vivo Antileishmanial Activity of Thioridazine

Insights into Ergosterol Peroxide’s Trypanocidal Activity

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