Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic  T. Cruzi Carriers

Morillo, Carlos A.; Waskin, Hetty; Sosa-Estáni, Sergio; Bangher, María del Carmen; Cuneo, Carlos Alberto; Milesi, Rodolfo; Mallagray, Marcelo; Apt, Werner; Beloscar, Juan; Gascón, Joaquim; Molina, Israel; Correa, Luis Eduardo Echeverría; Colombo, Hugo; Perez-Molina, José A.; Wyss, F; Meeks, Brandi; Bonilla, Laura; Gao, Peggy; Wei, Bo; McCarthy, Michael J.; Yusuf, Salim; Investigators, Stop-Chagas

doi:10.1016/j.jacc.2016.12.023

Cited by 243 publications

(215 citation statements)

References 37 publications

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“…Although several compounds with antichagasic activity and different potential molecular targets of the parasite have been described in the literature, no therapeutic alternatives have yet been able to replace nifurtimox and benznidazole. Some azoles previously used as antifungal drugs have generated high interest owing to their efficacy in animal models; however, recent clinical studies conducted with posaconazole (either alone or combined with benznidazole) and ravuconazole have shown that these treatments have no advantages over benznidazole monotherapy …”

Section: Introductionmentioning

confidence: 99%

“…Some azoles previously used as antifungal drugs have generated high interesto wing to their efficacy in animal models; however,r ecent clinical studies conducted with posaconazole (either alone or combined with benznidazole) and ravuconazole have shown that these treatments have no advantageso ver benznidazole monotherapy. [2][3][4] Fexinidazole,a nother nitroheterocycle currently studied as potentialtreatment for sleeping sickness, also seems promising in the field of antichagasic drugs. [5] Additionally,s ome highly active imidazo-and triazolopyrimidines, [6] acting through inhibition of the proteasome of severalp athogenic trypanosomatid protozoa( Trypanosoma, Leishmania), have been described.…”

Section: Introductionmentioning

confidence: 99%

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Antichagasic, Leishmanicidal, and Trichomonacidal Activity of 2‐Benzyl‐5‐nitroindazole‐Derived Amines

et al. 2018

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Three different series of new 5-nitroindazole derivatives-1-(ω-aminoalkyl)-2-benzylindazolin-3-ones (series A; ten compounds), 3-(ω-aminoalkoxy)-2-benzylindazoles (series B; four compounds) and 3-alkylamino-2-benzylindazoles (series C; five compounds)-have been synthesized and evaluated against the protozoan parasites Trypanosoma cruzi, Leishmania amazonensis, and Trichomonas vaginalis: etiological agents of Chagas disease, cutaneous leishmaniasis, and trichomoniasis, respectively. Many indazoles of series A, B, and C were efficient against T. cruzi. Some compounds in series A, after successfully passing the preliminary screening for epimastigotes, exhibited activity values against amastigotes of several T. cruzi strains that were better than or similar to those shown by the reference drug benznidazole and displayed low nonspecific toxicity against mammalian cells. On the other hand, preliminary studies against promastigotes of L. amazonensis showed high leishmanicidal activity for some derivatives of series A and C. With regard to activity against T. vaginalis, some indazoles of series B and C were rather efficient against trophozoites of a metronidazole-sensitive isolate and showed low nonspecific toxicities toward Vero cell cultures. Additionally, some of these compounds displayed similar activity against metronidazole-sensitive and resistant isolates, showing the absence of cross-resistance between these derivatives and the reference drug.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antichagasic, Leishmanicidal, and Trichomonacidal Activity of 2‐Benzyl‐5‐nitroindazole‐Derived Amines

et al. 2018

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“…CHAGASAZOL was not the only clinical trial testing the potential application of POS in Chagas Disease treatment. The clinical trial STOP-CHAGAS NCT01377480 [113] investigated if POS or POS plus BNZ were superior to BNZ monotherapy in the reduction of parasites load after 60 days of treatment and 360 days follow up. In this study, 120 subjects were randomly divided into the following groups: POS 400 mg twice a day; BNZ 200 mg and placebo, both twice a day; BNZ 200 mg and POS 400 mg, both twice a day; or placebo 10 mg. Two outcome stages were considered, the persistence of negative RT-PCR in day 180 and the maintenance of this response by the end of the study in day 360.…”

Section: Clinical Trialsmentioning

confidence: 99%

Efficacy and Safety of Chagas Disease Drug Therapy and Treatment Perspectives

Kawaguchi¹,

Cerqueira²,

MillanFachi³

et al. 2018

Chagas Disease - Basic Investigations and Challenges

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Chagas disease, also known as American trypanosomiasis, is a neglected disease caused by the protozoan parasite Trypanosoma cruzi. The disease affects about 6-7 million people worldwide, mostly in Latin America. Although Chagas disease was discovered more than 100 years ago, and the first treatments over 40, only 2 drugs were used to treat this pathology, it is still considered one of the neglected diseases. In this chapter, the subjects related to conventional etiological therapies, benznidazole and nifurtimox, such as the drug, the mechanism of action, the therapy schedule for treatment, efficacy and safety and their adverse effects will be discussed. Additionally, it will address alternative therapies of comorbidities related to the progression of Chagas' disease in patients with chronic disease, such as heart disease and dysfunction of the digestive system. Finally, novel pharmacological strategies and their related compounds will be reviewed accounting for their progression in pharmacological studies and their success rate.

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“…Posaconazole (Figure ) has been taken into phase II trials for the treatment of chronic Chagas disease. The purpose of the study was to determine whether posaconazole alone or in combination with benznidazole was superior to benznidazole monotherapy in eliminating T. cruzi ; however recent results have shown no advantages …”

Section: Current Treatments and Drug Developmentmentioning

confidence: 99%

Repurposing of Human Kinase Inhibitors in Neglected Protozoan Diseases

et al. 2017

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Human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis belong to a group of infectious diseases known as neglected tropical diseases and are induced by infection with protozoan parasites named trypanosomatids. Drugs in current use have several limitations, and therefore new candidate drugs are required. The majority of current therapeutic trypanosomatid targets are enzymes or cell‐surface receptors. Among these, eukaryotic protein kinases are a major group of protein targets whose modulation may be beneficial for the treatment of neglected tropical protozoan diseases. This review summarizes the finding of new hit compounds for neglected tropical protozoan diseases, by repurposing known human kinase inhibitors on trypanosomatids. Kinase inhibitors are grouped by human kinase family and discussed according to the screening (target‐based or phenotypic) reported for these compounds on trypanosomatids. This collection aims to provide insight into repurposed human kinase inhibitors and their importance in the development of new chemical entities with potential beneficial effects on the diseases caused by trypanosomatids.

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Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers

Cited by 243 publications

References 37 publications

Antichagasic, Leishmanicidal, and Trichomonacidal Activity of 2‐Benzyl‐5‐nitroindazole‐Derived Amines

Antichagasic, Leishmanicidal, and Trichomonacidal Activity of 2‐Benzyl‐5‐nitroindazole‐Derived Amines

Efficacy and Safety of Chagas Disease Drug Therapy and Treatment Perspectives

Repurposing of Human Kinase Inhibitors in Neglected Protozoan Diseases

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