Development of new dinuclear Fe(III) coordination compounds with in vitro nanomolar antitrypanosomal activity

2021 ◽  
Author(s):  
Felipe Figuerôa Moreira ◽  
Juliana de Araujo Portes ◽  
Nathalia Florencia Barros Azeredo ◽  
Christiane Fernandes ◽  
Adolfo Horn ◽  
...  
Keyword(s):  
Public Health ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Health Problem ◽  
Coordination Compounds ◽  
Public Health Problem ◽  
Neglected Tropical Disease ◽  
Major Public Health Problem ◽  
Protozoan Pathogen

Chagas disease is a neglected tropical disease caused by the protozoan pathogen Trypanosoma cruzi. The disease is the major public health problem affecting about 6 to 7 million people worldwide,...

Chagas disease and coumarins: a review of natural and synthetic coumarins as anti-Trypanosoma cruzi agents

2020 ◽  
Vol 21 ◽  
Author(s):  
Guilherme Arraché Gonçalves ◽  
Hugo Cerecetto ◽  
Gilsane Lino von Poser ◽  
Rômulo Faria Santos Canto ◽  
Vera Lucia Eifler-Lima
Keyword(s):  
Public Health ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Health Problem ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Public Health Problem ◽  
Neglected Tropical Disease ◽  
Limited Efficacy ◽  
Natural And Synthetic

The complexity of Chagas disease is still a challenge in endemic regions and an emergent public health problem in non-endemic countries. The causative agent of this neglected tropical disease, Trypanosoma cruzi, is mainly transmitted by triatomine vectors and possesses multiple epidemiologically important strains. Current chemotherapeutics are outdated and their limited efficacy is one of the major reasons for treatment discontinuation. In this context, it is urgent the development of novel, safe and economically accessible antichagasic drugs. Various classes of heterocycles and natural compounds have been described as potential antichagasic scaffolds, and coumarins are no exception. These versatile compounds have a wide spectrum of biological activities, and numerous natural and synthetic coumarins have been reported with antichagasic potential. The aim of this review is to discuss the available literature between 2001 and 2020 regarding natural and synthetic coumarins with anti-Trypanosoma cruzi activity. Moreover, some of the studies herein comprised are dedicated to the potential of coumarins to inhibit promising targets in Trypanosoma cruzi.

scholarly journals Tolerance of Benznidazole in Treatment of Chagas' Disease in Adults

2010 ◽  
Vol 54 (11) ◽  
pp. 4896-4899 ◽  
Author(s):  
María-Jesús Pinazo ◽  
José Muñoz ◽  
Elizabeth Posada ◽  
Paulo López-Chejade ◽  
Montserrat Gállego ◽  
...  
Keyword(s):  
Public Health ◽  
Side Effects ◽  
Trypanosoma Cruzi ◽  
European Country ◽  
Chagas Disease ◽  
Health Problem ◽  
Public Health Problem ◽  
Acute Stage ◽  
Chronic Stage

ABSTRACT Chagas’ disease is an emerging public health problem in areas where the disease is not endemic. Treatment with benznidazole has shown efficacy in the acute stage of the disease, but its efficacy in the chronic stage remains controversial, and unwanted side effects are more frequent and severe in adults than in children. This study describes the profile of side effects of benznidazole in a cohort of Trypanosoma cruzi-infected patients in a European country.

scholarly journals In Vitro and In Vivo Activities of E5700 and ER-119884, Two Novel Orally Active Squalene Synthase Inhibitors, against Trypanosoma cruzi

2004 ◽  
Vol 48 (7) ◽  
pp. 2379-2387 ◽  
Author(s):  
Julio A. Urbina ◽  
Juan Luis Concepcion ◽  
Aura Caldera ◽  
Gilberto Payares ◽  
Cristina Sanoja ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Public Health Problem ◽  
Squalene Synthase ◽  
Host Cells ◽  
In Vivo Studies ◽  
Inorganic Pyrophosphate ◽  
Orally Active

ABSTRACT Chagas' disease is a serious public health problem in Latin America, and no treatment is available for the prevalent chronic stage. Its causative agent, Trypanosoma cruzi, requires specific endogenous sterols for survival, and we have recently demonstrated that squalene synthase (SQS) is a promising target for antiparasitic chemotherapy. E5700 and ER-119884 are quinuclidine-based inhibitors of mammalian SQS that are currently in development as cholesterol- and triglyceride-lowering agents in humans. These compounds were found to be potent noncompetitive or mixed-type inhibitors of T. cruzi SQS with K i values in the low nanomolar to subnanomolar range in the absence or presence of 20 μM inorganic pyrophosphate. The antiproliferative 50% inhibitory concentrations of the compounds against extracellular epimastigotes and intracellular amastigotes were ca. 10 nM and 0.4 to 1.6 nM, respectively, with no effects on host cells. When treated with these compounds at the MIC, all of the parasite's sterols disappeared from the parasite cells. In vivo studies indicated that E5700 was able to provide full protection against death and completely arrested the development of parasitemia when given at a concentration of 50 mg/kg of body weight/day for 30 days, while ER-119884 provided only partial protection. This is the first report of an orally active SQS inhibitor that is capable of providing complete protection against fulminant, acute Chagas' disease.

scholarly journals Experimental Chemotherapy for Chagas Disease: A Morphological, Biochemical, and Proteomic Overview of Potential Trypanosoma cruzi Targets of Amidines Derivatives and Naphthoquinones

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Solange L. de Castro ◽  
Denise G. J. Batista ◽  
Marcos M. Batista ◽  
Wanderson Batista ◽  
Anissa Daliry ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Chronic Phase ◽  
Public Health Problem ◽  
Term Therapy ◽  
High Morbidity ◽  
Synthetic Compounds ◽  
Natural And Synthetic

Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately eight million individuals in Latin America and is emerging in nonendemic areas due to the globalisation of immigration and nonvectorial transmission routes. Although CD represents an important public health problem, resulting in high morbidity and considerable mortality rates, few investments have been allocated towards developing novel anti-T. cruzi agents. The available therapy for CD is based on two nitro derivatives (benznidazole (Bz) and nifurtimox (Nf)) developed more than four decades ago. Both are far from ideal due to substantial secondary side effects, limited efficacy against different parasite isolates, long-term therapy, and their well-known poor activity in the late chronic phase. These drawbacks justify the urgent need to identify better drugs to treat chagasic patients. Although several classes of natural and synthetic compounds have been reported to act in vitro and in vivo on T. cruzi, since the introduction of Bz and Nf, only a few drugs, such as allopurinol and a few sterol inhibitors, have moved to clinical trials. This reflects, at least in part, the absence of well-established universal protocols to screen and compare drug activity. In addition, a large number of in vitro studies have been conducted using only epimastigotes and trypomastigotes instead of evaluating compounds' activities against intracellular amastigotes, which are the reproductive forms in the vertebrate host and are thus an important determinant in the selection and identification of effective compounds for further in vivo analysis. In addition, due to pharmacokinetics and absorption, distribution, metabolism, and excretion characteristics, several compounds that were promising in vitro have not been as effective as Nf or Bz in animal models of T. cruzi infection. In the last two decades, our team has collaborated with different medicinal chemistry groups to develop preclinical studies for CD and investigate the in vitro and in vivo efficacy, toxicity, selectivity, and parasite targets of different classes of natural and synthetic compounds. Some of these results will be briefly presented, focusing primarily on diamidines and related compounds and naphthoquinone derivatives that showed the most promising efficacy against T. cruzi.

scholarly journals NEW WORLD LEISHMANIOSIS IN RUSSIAN TOURISTS WHO VISITED SOUTH AMERICAN COUNTRIES AND THE FIRST EXPERIENCE OF THE TREATMENT WITH PERU BALSAM

2017 ◽  
Vol 22 (2) ◽  
pp. 106-112
Author(s):  
A. M Bronshteyn ◽  
N. G Kochergin ◽  
N. A Malyshev ◽  
V. Ya Lashin ◽  
S. V Burova ◽  
...  
Keyword(s):  
Public Health ◽  
Cutaneous Leishmaniasis ◽  
Health Problem ◽  
New World ◽  
Folk Medicine ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
South American ◽  
Parasite Resistance ◽  
Local Species

Two cases of New World cutaneous leishmaniasis acquired by Russian tourists in Peru and possibly in Bolivia are presented. L. viannia ( L.braziliensis complex) was identified in Liverpool School of Tropical medicine in the patient travelled to Bolivia. The present study aimed to investigate Balsamum peruvianum one of the product of folk medicine of Indians of Amazon region against local species of Leishmania resulted in healing the ulcers. Leishmaniasis is a major public health problem, and the alarming spread of parasite resistance has increased the importance of discovering new therapeutic products.

Leprosy (Hansen’s disease)

2010 ◽  
pp. 836-848
Author(s):  
Diana N.J. Lockwood
Keyword(s):  
Public Health ◽  
Chronic Granulomatous Disease ◽  
Health Problem ◽  
Disease Transmission ◽  
Public Health Problem ◽  
Mycobacterium Leprae ◽  
Granulomatous Disease ◽  
Important Public Health Problem ◽  
Important Public Health

Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae, an acid-fast intracellular organism not yet cultivated in vitro. It is an important public health problem worldwide, with an estimated 4 million people disabled by the disease. Transmission of M. leprae is only partially understood, but untreated lepromatous patients discharge abundant organisms from their nasal mucosa into the environment....

scholarly journals Smoking in Latin America: a major public health problem

1998 ◽  
Vol 14 (suppl 3) ◽  
pp. S109-S115 ◽  
Author(s):  
Vera Luiza da Costa e Silva ◽  
Sergio Koifman
Keyword(s):  
Public Health ◽  
Latin America ◽  
Latin American ◽  
Health Problem ◽  
Public Health Problem ◽  
Lung Cancer Mortality ◽  
Developed Countries ◽  
Major Public Health Problem ◽  
Tobacco Epidemic ◽  
Latin American Countries

Smoking has become a major public health problem in Latin America, and its scope varies from country to country. Despite difficulties in obtaining methodologically consistent data for the region, we analyzed the results from prevalence surveys in 14 Latin American countries. Smoking prevalence among men varied from 24.1% (Paraguay) to 66.3% (Dominican Republic) and among women from 5.5% (Paraguay) to 26,6% (Uruguay). By applying point prevalence data to the stage model of the tobacco epidemic in developed countries, we concluded that the Latin American countries are in stage 2, i.e., with a clearly rising prevalence among men, a prevalence for women that is beginning to increase, and mortality attributable to smoking among men still not reflecting peak prevalence. None of the countries analyzed appeared to have reached stage 3, in which one observes a downward trend in prevalence of smoking among men and peak prevalence among women, with broad impact on tobacco-related mortality. The only exception appears to be Paraguay, which is still emerging from stage 1, i.e., with low prevalence rates among men, too. Nevertheless, high lung cancer mortality rates in Uruguay and Argentina are comparable to those of the developed countries.

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