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

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 Current chemotherapeutics are outdated and their limited efficacy is one of the major reasons for treatment discontinuation.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.

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

Dalton Transactions ◽

10.1039/d1dt01048d ◽

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,...

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Tolerance of Benznidazole in Treatment of Chagas' Disease in Adults

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00537-10 ◽

2010 ◽

Vol 54 (11) ◽

pp. 4896-4899 ◽

Cited By ~ 114

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.

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

Molecular Biology International ◽

10.4061/2011/306928 ◽

2011 ◽

Vol 2011 ◽

pp. 1-13 ◽

Cited By ~ 10

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.

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Arthritis and Benznidazole: More Closely Related than We Thought

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04078-14 ◽

2014 ◽

Vol 59 (1) ◽

pp. 727-729 ◽

Cited By ~ 7

Author(s):

E. Aldasoro ◽

M. J. Pinazo ◽

I. Oliveira ◽

J. Munoz ◽

E. Posada ◽

...

Keyword(s):

Public Health ◽

Chagas Disease ◽

Health Problem ◽

Parasitic Infection ◽

Public Health Problem ◽

Drug Reactions ◽

Content Type ◽

Significant Public Health Problem ◽

Rare Side Effect ◽

Significant Public Health

ABSTRACTChagas disease is a parasitic infection that leads to a significant public health problem in countries where the disease is endemic and where it is nonendemic. Benznidazole is the most commonly used drug for the etiological treatment of Chagas disease. Patients treated with benznidazole suffer frequent adverse drug reactions. Although arthralgia is common, arthritis has been reported as a very rare side effect. The objective of this study was to describe arthritis in a cohort ofTrypanosoma cruzi-infected patients treated with benznidazole.

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DISTRIBUTION OF TRIATOMINES (HETEROPTERA: REDUVIIDAE) ASSOCIATED WITH HUMAN HABITATION AND POTENTIAL RISK AREAS IN SIX STATES OF THE MEXICAN REPUBLIC

BIOCYT Biología Ciencia y Tecnología ◽

10.22201/fesi.20072082.2012.5.76093 ◽

2020 ◽

Vol 5 ◽

Author(s):

José Ismael Benítez-Alva ◽

Herón Huerta ◽

Juan Luis Téllez-Rendón

Keyword(s):

Public Health ◽

Latin America ◽

Trypanosoma Cruzi ◽

Potential Risk ◽

Health Problem ◽

Natural Infection ◽

Public Health Problem ◽

Distribution Maps ◽

Risk Areas ◽

Human Habitation

Chagas disease is a real public health problem in Latin America, caused by the flagellate protozoan Trypanosoma cruzi and described by Carlos Chagas in 1909. T. cruzi is transmitted by bloodsucking insects of the subfamily Triatominae which thrive in sylvatic, peridomestic, and domestic habitats, being in the latter two a potential risk to public health because of their role as vectors. We review the distribution of triatomines associated with human habitation and their natural infection with T. cruzi from the states of Aguascalientes, Chiapas, Guerrero, Jalisco, Michoacán, and Oaxaca. Based on samples received in the Laboratory of Entomology of the Institute of Epidemiological Diagnosis and Reference (InDRE-SSA) during the period 2006 to 2010, distribution maps and stratification of potential areas of risk were made. A total of 1910 specimens of seven species of triatomines were identified. Triatoma barberi, Meccus longipennis and M. pallidipennis were the species with the highest rate of infection with T. cruzi; M. pallidipennis and T. dimidiata were the most widely distributed species.

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Insights from mathematical modelling and quantitative analysis on the proposed 2030 goals for trachoma

Gates Open Research ◽

10.12688/gatesopenres.13086.2 ◽

2021 ◽

Vol 3 ◽

pp. 1721

Author(s):

Keyword(s):

Public Health ◽

Quantitative Analysis ◽

Health Problem ◽

Statistical Models ◽

Public Health Problem ◽

World Health ◽

Neglected Tropical Disease ◽

Monitoring Tools ◽

Health Organization ◽

Trachomatous Trichiasis

Trachoma is a neglected tropical disease and the leading infectious cause of blindness worldwide. The current World Health Organization goal for trachoma is elimination as a public health problem, defined as reaching a prevalence of trachomatous inflammation-follicular below 5% in children (1-9 years) and a prevalence of trachomatous trichiasis in adults below 0.2%. Current targets to achieve elimination were set to 2020 but are being extended to 2030. Mathematical and statistical models suggest that 2030 is a realistic timeline for elimination as a public health problem in most trachoma endemic areas. Although the goal can be achieved, it is important to develop appropriate monitoring tools for surveillance after having achieved the elimination target to check for the possibility of resurgence. For this purpose, a standardized serological approach or the use of multiple diagnostics in complement would likely be required.

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Antimicrobials from Venomous Animals: An Overview

Molecules ◽

10.3390/molecules25102402 ◽

2020 ◽

Vol 25 (10) ◽

pp. 2402 ◽

Cited By ~ 4

Author(s):

Tania Yacoub ◽

Mohamad Rima ◽

Marc Karam ◽

Jean-Marc Sabatier ◽

Ziad Fajloun

Keyword(s):

Public Health ◽

Health Problem ◽

Antimicrobial Agents ◽

Biological Activities ◽

Public Health Problem ◽

Antimicrobial Activities ◽

Mechanisms Of Action ◽

Natural Agents ◽

Venomous Animals ◽

Animal Venoms

The inappropriate or excessive use of antimicrobial agents caused an emerging public health problem due to the resulting resistance developed by microbes. Therefore, there is an urgent need to develop effective antimicrobial strategies relying on natural agents with different mechanisms of action. Nature has been known to offer many bioactive compounds, in the form of animal venoms, algae, and plant extracts that were used for decades in traditional medicine. Animal venoms and secretions have been deeply studied for their wealth in pharmaceutically promising molecules. As such, they were reported to exhibit many biological activities of interest, such as antibacterial, antiviral, anticancer, and anti-inflammatory activities. In this review, we summarize recent findings on the antimicrobial activities of crude animal venoms/secretions, and describe the peptides that are responsible of these activities.

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