scholarly journals Synthesis of New Selenides-1,2,3-Triazoles with Potential Activity against Trypanossoma cruzi

2020 ◽  
Vol 2 (1) ◽  
pp. 22
Author(s):  
Beatrice Brasil ◽  
Ingrid Chipoline ◽  
Vanessa Nascimento
Keyword(s):  
Chagas Disease ◽  
Treatment Time ◽  
World Health ◽  
Neglected Diseases ◽  
Hybridization Technique ◽  
Target Molecules ◽  
Potential Activity ◽  
Health Organization ◽  
The Individual

Chagas disease, considered by the World Health Organization as a neglected tropical disease, is responsible for the deaths of more than 10,000 people annually. The main drugs used to overcome the disease, Benzonidazole and Nifurtimox, besides being old, have limitations regarding the adverse effects related to the treatment time and, consequently, their toxicity. Therefore, the need for a new drug to be used against this disease becomes evident. The classes of organoselenium and aromatic heterocycles 1,2,3-triazoles are promising for the issue of the profile of both classes for further evaluation against Trypanossoma cruzi, since the known chemistry and antiparasitic activity of both have already been described. In this work, the molecular hybridization technique was used in order to combine the individual bioactive protozoan that causes Chagas disease. The methodology used was based on works described in the literature. Initially, benzene azides were synthesized from commercial anilines, while ethynyl(phenyl)selane came from different aromatic diselenides. With these intermediates, a 1,3-dipolar cycle-addition was performed to obtain the new target molecules 1-phenyl-4-(phenylselanyl)-1H-1,2,3-triazoles, with moderate to good yields ranging from 52 to 75%. The characterization of the final molecules is in process and, when finished, they will be sent for evaluation of biological activity. It is possible to conclude that the method used is simple and easy to access, an important factor for potential drugs against neglected diseases. After the assessment of bioactivity, it will be possible to identify the efficiency of these substances, as well as, if necessary, the optimization of their structure.

scholarly journals Capsaicin inhibits arginine kinase and exerts anti-Trypanosoma cruzi activity

2020 ◽  
Author(s):  
Edward A. Valera-Vera ◽  
Chantal Reigada ◽  
Melisa Sayé ◽  
Fabio A. Digirolamo ◽  
Mariana R. Miranda ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Stress Responses ◽  
Mammalian Cells ◽  
Arginine Kinase ◽  
Chronic Phase ◽  
New Drugs ◽  
World Health ◽  
Neglected Diseases ◽  
Health Organization

ABSTRACTTrypanosoma cruzi is the causative agent of Chagas disease, considered within the list of twenty neglected diseases according to the World Health Organization. There are only two therapeutic drugs for Chagas disease, both of them unsuitable for the chronic phase, therefore the development of new drugs is a priority.T. cruzi arginine kinase (TcAK) is a promising drug target since it is absent in humans and it is involved in cellular stress responses. In a previous study from our laboratory, possible TcAK inhibitors were identified through computer simulations, resulting in the best-scoring compounds cyanidin derivatives and capsaicin. Considering these results, in this work we evaluate the effect of capsaicin on TcAK activity and its trypanocidal effect. Although capsaicin produced a weak inhibition on the recombinant TcAK activity (IC50 ≈ 800 µM), it had a strong trypanocidal effect on epimastigotes and trypomastigotes (IC50 = 6.26 µM and 0.26 µM, respectively) being 20-fold more active on trypomastigotes than mammalian cells. Epimastigotes that overexpress TcAK were 37% more resistant to capsaicin than wild type parasites, suggesting that trypanocidal activity could be due, in part, to the enzyme inhibition. However, the difference between the concentrations at which the enzyme is inhibited and the parasite death is caused implies the presence of other targets. In this sense, the prohibitin-2 and calmodulin were identified as other possible capsaicin targets. Capsaicin is a strong and selective trypanocidal agent active in nanomolar concentrations, with an IC50 57-fold lower than benznidazole, the drug currently used for treating Chagas disease.

Synthesis of New Thiosemicarbazones and Semicarbazones Containing the 1,2,3-1H-triazole-isatin Scaffold: Trypanocidal, Cytotoxicity, Electrochemical Assays, and Molecular Docking

2019 ◽  
Vol 15 (3) ◽  
pp. 240-256 ◽  
Author(s):  
Bianca N.M. Silva ◽  
Policarpo A. Sales Junior ◽  
Alvaro J. Romanha ◽  
Silvane M.F. Murta ◽  
Camilo H.S. Lima ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Docking Studies ◽  
World Health ◽  
Neglected Diseases ◽  
Alkyl Aryl ◽  
Development Of Resistance ◽  
Health Organization

Background: Chagas disease, also known as American trypanosomiasis, is classified as one of the 17 most important neglected diseases by the World Health Organization. The only drugs with proven efficacy against Chagas disease are benznidazole and nifurtimox, however both show adverse effects, poor clinical efficacy, and development of resistance. For these reasons, the search for new effective chemical entities is a challenge to research groups and the pharmaceutical industry. Objective: Synthesis and evaluation of antitrypanosomal activities of a series of thiosemicarbazones and semicarbazones containing 1,2,3-1H triazole isatin scaffold. Method: 5&'-(4-alkyl/aryl)-1H-1,2,3-triazole-isatins were prepared by Huisgen 1,3-dipolar cycloaddition and the thiosemicarbazones and semicarbazones were obtained by the 1:1 reactions of the carbonylated derivatives with thiosemicarbazide and semicarbazide hydrochloride, respectively, in methanol, using conventional reflux or microwave heating. The compounds were assayed for in vitro trypanocidal activity against Trypanosoma cruzi, the aetiological agent of Chagas disease. Beyond the thio/semicarbazone derivatives, isatin and triazole synthetic intermediates were also evaluated for comparison. Results: A series of compounds were prepared in good yields. Among the 37 compounds evaluated, 18 were found to be active, in particular thiosemicarbazones containing a non-polar saturated alkyl chain (IC50 = 24.1, 38.6, and 83.2 &µM; SI = 11.6, 11.8, and 14.0, respectively). To further elucidate the mechanism of action of these new compounds, the redox behaviour of some active and inactive derivatives was studied by cyclic voltammetry. Molecular docking studies were also performed in two validated protein targets of Trypanosoma cruzi, i.e., cruzipain (CRZ) and phosphodiesterase C (TcrPDEC). Conclusion: A class of thio/semicarbazones structurally simple and easily accessible was synthesized. Compounds containing thiosemicarbazone moieties showed the best results in the series, being more active than the corresponding semicarbazones. Our results indicated that the activity of these compounds does not originate from an oxidation-reduction pathway but probably from the interactions with trypanosomal enzymes.

Zinc 1,2,4-triazolo[1,5-a]pyrimidine complexes: synthesis, structural characterization and their effect against Chagas disease

2021 ◽  
Vol 17 ◽  
Author(s):  
José M. Méndez-Arriaga ◽  
Erika Rubio-Mirallas ◽  
Miguel Quirós ◽  
Manuel Sánchez-Moreno
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
New Drugs ◽  
World Health ◽  
Neglected Diseases ◽  
X Ray Diffraction ◽  
X Ray ◽  
Health Organization ◽  
The Third World

Background: The World Health Organization catalogues illnesses such as Chagas disease as neglected diseases, due the low investment in new drugs to fight them. The search for novel and non-side effects anti-parasitic compounds is one of the urgent needs of the Third World. The use of triazolopyrimidines and their metal complexes have demonstrated hopeful results in this field. Objective: This work studies the antiparasitic efficacy against Trypanosoma cruzi strains of a series of zinc triazolopyrimidine complexes. Method: A series of Zn complexes has been synthesized by the reaction between the triazolopyrimidine derivatives 7-amino-1,2,4-triazolo[1,5-a]pyrimidine (7atp) and 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp) with Zn(SO4) • 7H2O, ZnCl2, and Zn(NO3)2 • 6H2O salts. The complexes have been analyzed by spectroscopic and thermal assays and X-ray diffraction methods have been used to dilucidate the crystalline structure of one of them. The antiparasitic efficacy was tested in vitro against Trypanosoma cruzi to compare the trypanocidal effect of different ligands and counteranions to fight Chagas disease. Results: The efficacy of these compounds against Trypanosoma cruzi has also been tested to compare the influence of different ligands and counteranions on the trypanocidal effect against Chagas disease. Conclusion: Antiproliferative tests corroborate the synergistic trypanocidal effect of the triazolopyrimidine coordination complexes.

The relevance of dietetic approach of Ayurveda from the perspective of COVID-19 pandemic

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 748-752
Author(s):  
Swapnali Khabade ◽  
Bharat Rathi ◽  
Renu Rathi
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Healthy Person ◽  
World Health ◽  
Physical And Mental Health ◽  
Leading Role ◽  
Global Pandemic ◽  
The People ◽  
The World ◽  
Health Organization ◽  
The Individual

A novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes severe acute respiratory syndrome and spread globally from Wuhan, China. In March 2020 the World Health Organization declared the SARS-Cov-2 virus as a COVID- 19, a global pandemic. This pandemic happened to be followed by some restrictions, and specially lockdown playing the leading role for the people to get disassociated with their personal and social schedules. And now the food is the most necessary thing to take care of. It seems the new challenge for the individual is self-isolation to maintain themselves on the health basis and fight against the pandemic situation by boosting their immunity. Food organised by proper diet may maintain the physical and mental health of the individual. Ayurveda aims to promote and preserve the health, strength and the longevity of the healthy person and to cure the disease by properly channelling with and without Ahara. In Ayurveda, diet (Ahara) is considered as one of the critical pillars of life, and Langhana plays an important role too. This article will review the relevance of dietetic approach described in Ayurveda with and without food (Asthavidhi visheshaytana & Lanhgan) during COVID-19 like a pandemic.

Engaging older people in healthy and active lifestyles: a systematic review

2015 ◽  
Vol 36 (10) ◽  
pp. 2036-2060 ◽  
Author(s):  
JULIA MENICHETTI ◽  
PIETRO CIPRESSO ◽  
DARIO BUSSOLIN ◽  
GUENDALINA GRAFFIGNA
Keyword(s):  
Systematic Review ◽  
Health Promotion ◽  
World Health ◽  
Active Ageing ◽  
Individual Level ◽  
Active Lifestyles ◽  
Health Organization ◽  
The Individual ◽  
Health Promotion Interventions ◽  
Older Citizens

ABSTRACTIn 2002, the World Health Organization emphasised the concept of active ageing to manage and increase the last third of life. Although many efforts have been made to optimise treatment management, less attention has been paid to health promotion initiatives. To date, few shared guidelines exist that promote an active life in healthy older targets. To fill this gap, we conducted a systematic review to map health promotion interventions that targeted an active and healthy ageing among older citizens. Articles containing the key term active ageing and seven synonyms were searched for in the electronic databases. Because we were interested in actions aimed to promote healthier lifestyles, we connected the string with the term health. A total of 3,918 titles were retrieved and 20 articles were extracted. Twelve of the 20 studies used group interventions, five interventions targeted the individual level and three interventions targeted the community level. Interventions differed for the health focus of the programmes, which ranged from physical activity interventions to social participation or cognitive functioning. Most of the studies aimed to act on psychological components. The review suggests that different interventions promoted for active ageing are effective in improving specific healthy and active lifestyles; however, no studies were concerned directly with a holistic process of citizen health engagement to improve long-term outcomes.

Indeterminate Chagas’ disease: Trypanosoma cruzi strain and re-infection are factors involved in the progression of cardiopathy

2003 ◽  
Vol 104 (4) ◽  
pp. 415-420 ◽  
Author(s):  
Juan M. BUSTAMANTE ◽  
Héctor W. RIVAROLA ◽  
Alicia R. FERNÁNDEZ ◽  
Julio E. ENDERS ◽  
Ricardo FRETES ◽  
...  
Keyword(s):  
Survival Rate ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Infected Group ◽  
World Health ◽  
Cardiac Lesions ◽  
Health Organization ◽  
Host Parasite ◽  
Β Adrenergic Receptors ◽  
First Time

Chagas' disease is caused by Trypanosoma cruzi, which is transmitted by reduviid bugs. The World Health Organization has estimated that about 16–18 million people in the Americas are infected, and that more than 100 million are at risk. In the present study we have used a murine model to analyse if particular T. cruzi strains (Tulahuen strain and SGO-Z12 isolate from a chronic patient) and/or re-infection may determine, during the indeterminate phase of experimental Chagas' disease, changes that could explain the different evolution of cardiac lesions. Re-infected mice reached higher parasitaemias than those infected for the first time. The survival in the indeterminate phase of mice infected with Tulahuen strain was 50.0%, while the SGO-Z12-infected group presented a significantly higher survival rate (77.1%; P<0.01). The SGO-Z12-re-infected group showed a survival rate (70.9%) significantly higher than that of the Tulahuen-re-infected group (37.0%; P<0.01). Electrocardiographic abnormalities were found in 66% of Tulahuen-infected mice, while in SGO-Z12-infected group such abnormalities were found in only 36% of animals (P<0.01). The two groups exhibited similar percentages of electrocardiographic dysfunction on re-infection, although intraventricular blocks were more frequent in Tulahuen-re-infected mice (P<0.01). Hearts from infected or re-infected mice with either parasite showed mononuclear infiltrates. The SGO-Z12-re-infected and Tulahuen-re-infected groups exhibited a significantly diminished affinity (P<0.05) and a significantly increased density (P<0.05) of cardiac β-adrenergic receptors compared with the infected and non-infected groups. The indeterminate phase of Chagas' disease is defined as a prolonged period that is clinically silent, but the present findings show that different T. cruzi strains and re-infection are able to alter the host–parasite equilibrium, and these factors may be responsible for inducing progressive cardiopathy.

Pharmacogenetics of Metformin

2021 ◽  
Vol 1 (6) ◽  
pp. 123-129
Author(s):  
Alrahman Joneri
Keyword(s):  
American Diabetes Association ◽  
Glucose Utilization ◽  
Medical Condition ◽  
World Health ◽  
First Line ◽  
Glucose Levels ◽  
Normal Limits ◽  
The World ◽  
Health Organization ◽  
The Individual

Hyperglycemia is a medical condition in which an increase in glucose levels in the blood exceeds normal limits. Hyperglycemia is one of the typical signs of diabetes mellitus (DM). The World Health Organization (WHO) predicts an increase in the number of people with DM which is a global health threat. Diabetes is the leading cause of kidney failure, and the leading cause of heart disease and stroke, in adults. Metformin, which is a biguanide group, is recommended by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes as the first-line oral therapy for DM and is the most widely used oral medication worldwide. Metformin can also increase peripheral glucose utilization and ultimately decrease the production of fatty acids and triglycerides. Some of the individual differences that underlie the variation in response to metformin.

Implementing the Sphere Project’s standards for patient’s healthcare rights in the disaster zone: The experience of the Israeli field hospital in post-quake Nepal

2021 ◽  
Vol 16 (1) ◽  
pp. 59-66
Author(s):  
Deganit Kobliner-Friedman, RN, MPH ◽  
Ofer Merin, MD ◽  
Eran Mashiach, MD ◽  
Reuven Kedar, MD ◽  
Shai Schul, MHA ◽  
...  
Keyword(s):  
Disaster Response ◽  
Sexual Exploitation ◽  
World Health ◽  
Field Hospital ◽  
Medical Teams ◽  
Health Organization ◽  
The Individual ◽  
The Right ◽  
Israel Defense Forces ◽  
Privacy And Confidentiality

Emergency medical teams (EMTs) encounter chaos upon arriving at the scene of a disaster. Rescue efforts are utilitarian and focus on providing the technical aspects of medical care in order to save the most lives at the expense of the individual. This often neglects the basic healthcare rights of the patient. The Sphere Project was initiated to develop universal humanitarian standards for disaster response.The increase in the number of EMTs led the World Health Organization (WHO) to organize standards for disaster response. In 2016, the WHO certified the Israel Defense Forces Field Hospital (IDF-FH) as the first to be awarded the highest level of accreditation (EMT-3). This paper presents the IDF-FH’s efforts to protect the patient’s healthcare rights in a disaster zone based on the Sphere Principles.These core Sphere Principles include the right to professional medical treatment; the right to dignity, privacy, and confidentiality; the right for information in an understandable language; the right to informed consent; the obligation to maintain private medical records; the obligation to adhere to universal ethical standards, to respect culture and custom and to care for vulnerable populations; the right to protection from sexual exploitation and violence; and the right to continued treatment.

scholarly journals Myelodysplastic syndrome: classification and prognostic systems

2011 ◽  
pp. 25-33
Author(s):  
Rosangela Invernizzi ◽  
Agnese Filocco
Keyword(s):  
Clinical Information ◽  
Scoring Systems ◽  
Classification Systems ◽  
World Health ◽  
Individual Risk ◽  
Information Classification ◽  
Definition Of ◽  
Health Organization ◽  
The Individual ◽  
Prognostic Scoring Systems

Myelodysplastic syndromes (MDS) are acquired clonal disorders of hematopoiesis, that are characterized most frequently by normocellular or hypercellular bone marrow specimens, and maturation that is morphologically and functionally dysplastic. MDS constitute a complex hematological problem: differences in disease presentation, progression and outcome have made it necessary to use classification systems to improve diagnosis, prognostication and treatment selection. On the basis of new scientific and clinical information, classification and prognostic systems have recently been updated and minimal diagnostic criteria forMDS have been proposed by expert panels. In addition, in the last few years our ability to define the prognosis of the individual patient with MDS has improved. In this paper World Health Organization (WHO) classification refinements and recent prognostic scoring systems for the definition of individual risk are highlighted and current criteria are discussed. The recommendations should facilitate diagnostic and prognostic evaluations in MDS and selection of patients for new effective targeted therapies.

scholarly journals THE HUMAN RIGHT TO HEALTH: A RETROSPECTIVE ANALYSIS AFTER 70 YEARS OF INTERNATIONAL RECOGNITION

2018 ◽  
pp. 24-42
Author(s):  
MARÍA DALLI
Keyword(s):  
Human Rights ◽  
Right To Health ◽  
World Health ◽  
Health Coverage ◽  
Human Right ◽  
The Sustainable Development ◽  
Cultural Rights ◽  
Health Organization ◽  
The Individual ◽  
The Right

In 1948, the General Assembly of the United Nations adopted the first international text recognising universal human rights for all; the Universal Declaration of Human Rights. Article 25 recognises the right to an adequate standard of living, which includes the right to health and medical care. On the occasion of the 70th anniversary of the Declaration, this article presents an overview of the main developments that have been made towards understanding the content and implications of the right to health, as well as an analysis of some specific advancements that aim to facilitate the enforcement thereof. These include: a) the implication of private entities as responsible for right to health obligations; b) the Universal Health Coverage goal, proposed by the World Health Organization and included as one of the Sustainable Development Goals; and c) the individual complaints mechanism introduced by the Optional Protocol to the International Covenant on Economic, Social and Cultural Rights (adopted on the 10th December 2008, 60 years after the UDHR).

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