Antileishmanial activity evaluation of thiazolidine-2,4-dione against Leishmania infantum and Leishmania braziliensis.

Leishmaniasis is responsible for approximately 65,000 annual deaths. Despite the mortality data, drugs available for the treatment of patients are insufficient and have moderate therapeutic efficacy in addition to serious adverse effects, which makes the development of new drugs urgent. To achieve this goal, the integration of kinetic and DSF assays against parasitic validated targets, along with phenotypic assays, can help the identification and optimization of bioactive compounds. Pteridine reductase 1 (PTR1), a validated target in Leishmania sp., is responsible for the reduction of folate and biopterin to tetrahydrofolate and tetrahydrobiopterin, respectively, both of which are essential for cell growth. In addition to the in vitro evaluation of 16 thiazolidine-2,4-dione derivatives against Leishmania major PTR1 (LmPTR1), using the differential scanning fluorimetry (ThermoFluor®), phenotypic assays were employed to evaluate the compound effect over Leishmania braziliensis (MHOM/BR/75/M2903) and Leishmania infantum (MHOM/BR/74/PP75) promastigotes viability. The ThermoFluor® results show that thiazolidine-2,4-dione derivatives have micromolar affinity to the target and equivalent activity on Leishmania cells. 2b is the most potent compound against L. infantum (EC50 = 23.45 ± 4.54 µM), whereas 2a is the most potent against L. braziliensis (EC50 = 44.16 ± 5.77 µM). This result suggests that lipophilic substituents on either-meta and/or-para positions of the benzylidene ring increase the potency against L. infantum. On the other hand, compound 2c (CE50 = 49.22 ± 7.71 µM) presented the highest selectivity index.

A novel antiplasmodial compound: integration of in silico and in vitro assays.

Malaria is a disease caused by Plasmodium genus. which P. falciparum is responsible for the most severe form of the disease, cerebral malaria. In 2018, 405,000 people died of malaria. Antimalarial drugs have serious adverse effects and limited efficacy due to multidrug-resistant strains. One way to overcome these limitations is the use of computational approaches for prioritizing candidates to phenotypic assays and/or in vitro assays against validated targets. Plasmodium falciparum Enoyl-ACP reductase (PfENR) is noteworthy because it catalyzes the rate-limiting step of the biosynthetic pathway of fatty acid. Thus, the study aimed to identify potential PfENR inhibitors by ligand (2D molecular similarity and pharmacophore models) and structure-based virtual screening (molecular docking). 2D similarity-based virtual screening using Tanimoto Index (> 0.45) selected 29,236 molecules from natural products subset available in ZINC database (n = 181,603). Next, 10 pharmacophore models for PfENR inhibitors were generated and evaluated based on the internal statistical parameters from GALAHAD™ and ROC/AUC curve. These parameters selected a suitable pharmacophore model with one hydrophobic center and two hydrogen bond acceptors. The alignment of the filtered molecules on best pharmacophore model resulted in the selection of 10,977 molecules. These molecules were directed to the docking-based virtual screening by AutoDock Vina 1.1.2 program. These strategies selected one compound to phenotypic assays against parasite. ZINC630259 showed EC50 = 0.12 ± 0.018 µM in antiplasmodial assays and selective index similar to other antimalarial drugs. Finally, MM/PBSA method showed stability of molecule within PfENR binding site (ΔGbinding=-57.337 kJ/mol).Communicated by Ramaswamy H. Sarma.

Identification of novel antiplasmodial compound by hierarquical virtual screening and in vitro assays.

Malaria is an infectious disease caused by protozoa of the genus Plasmodium spp. with approximately 219 million cases in 2017. P. falciparum is main responsible for the most severe form of the disease, cerebral malaria. Despite of public health impacts, chemotherapy against malaria is still limited due to the emergence of drug resistance cases used in monotherapy and combination therapies. Thus, the development of new antimalarial drugs becomes emergency. One way of achieve this goal is to explore essential and/or unique therapeutic targets of the parasite, or at least sufficiently different to ensure selective inhibition. Enoil-ACP reductase (ENR) is a NADH-dependent enzyme responsible for the limiting step of the type II fatty acid biosynthetic pathway (FAS II). Thus, pharmacophore and docking based virtual screening were applied to prioritize molecules for in vitro assays against P. falciparum W2 strain. The application of successive filters at OOCC database (n = 618) resulted in the identification of one molecule (13) (EC50 = 0.098 ± 0.021 µM) with similar biological activity to artemether. The molecule 13 is a typical drug repurposing case due to previous other approved therapeutic uses on Chinese medicine as a non-specific cholinergic antagonist, thus it could be accelerated the drug development process. Additionally, molecular dynamics studies were used to confirm stability of the molecular interactions identified by molecular docking. Thus, representative structures of P. falciparum ENR can be used in a study to propose new derivatives for evaluation of biological activity in vitro and in vivo. Communicated by Ramaswamy H. Sarma.

Uso irracional de medicamentos na pandemia do Covid-19: revisão integrativa / Irrational use of medicines in the Covid-19 pandemic: integrative review / Uso irracional de medicamentos en la pandemia de Covid-19: revisión integradora

Os medicamentos são uma importante fonte tática de ação em saúde, quando usados para prevenção, alívio, diagnóstico ou cura de algumas enfermidades. Entretanto, apesar dos benefícios de tratar diversas doenças, os medicamentos podem trazer consigo riscos, como efeitos colaterais graves à saúde do usuário, além de possibilitar a resistência microbiana. O consumo excessivo de medicamentos sem prescrição é considerado um grande problema na saúde pública e vem sendo acentuado desde o período pandêmico da COVID-19 disso, partindo do princípio de que os fármacos podem desencadear reações adversas e apresentar danos à saúde, o objetivo deste artigo é discutir o uso irracional de medicamentos e destacar os medicamentos mais utilizados pela população na pandemia da COVID-19. Trata-se de um estudo de revisão integrativa da literatura. Foi realizado um levantamento bibliográfico de 12 artigos científicos do ano de 2020 a 2022. Destaca- se que o uso indevido de medicamentos consiste em uma prática corriqueira na sociedade e a automedicação durante o período da pandemia apresentou-se como um risco à população. Os medicamentos mais citados na pesquisa foram a azitromicina e a ivermectina.

Medications are an important tactical source of health action, when used for prevention, relief, diagnosis or cure of some diseases. However, despite the benefits of treating various diseases, medications can bring with them risks, such as serious side effects to the user's health, as well as enabling microbial resistance. The excessive consumption of non-prescription drugs is considered a major problem in public health and has been accentuated since the pandemic period of COVID-19 of this, assuming that drugs can trigger adverse reactions and present damage to health, the aim of this article is to discuss the irrational use of medicines and highlight the most commonly used drugs by the population in the pandemic of COVID-19. This is an integrative literature review study. A literature survey of 12 scientific articles from the year 2020 to 2022 was conducted. It is noteworthy that the misuse of medicines is a common practice in society and self-medication during the pandemic period presented itself as a risk to the population. The most cited drugs in the survey were azithromycin and ivermectin.

Los medicamentos son una importante fuente táctica de acción sanitaria, cuando se utilizan para prevenir, aliviar, diagnosticar o curar algunas enfermedades. Sin embargo, a pesar de los beneficios en el tratamiento de diversas enfermedades, los medicamentos pueden traer consigo riesgos, como graves efectos secundarios para la salud del usuario, además de posibilitar la resistencia microbiana. El consumo excesivo de medicamentos de venta libre es considerado un gran problema de salud pública y se ha acentuado desde el período de la pandemia de COVID-19 de esto, asumiendo que los medicamentos pueden desencadenar reacciones adversas y presentar daños a la salud, el objetivo de este artículo es discutir el uso irracional de medicamentos y destacar los fármacos más utilizados por la población en la pandemia de COVID-19. Se trata de un estudio de revisión bibliográfica integradora. Se realizó un estudio bibliográfico de 12 artículos científicos del año 2020 al 2022. Se destaca que el uso indebido de medicamentos es una práctica común en la sociedad y la automedicación durante el período pandémico se presentó como un riesgo para la población. Los medicamentos más citados en la encuesta fueron la azitromicina y la ivermectina.

Uso da aromaterapia no tratamento dos transtornos de ansiedade e depressão: uma revisão integrativa / Use of aromatherapy in the treatment of anxiety and depression disorders: an integrative review / Uso de la aromaterapia en el tratamiento de los trastornos de ansiedad y depresión: una revisión integradora

Os episódios envolvendo transtornos comportamentais como a ansiedade e a depressão têm aumentado ao longo dos últimos decênios. Ambos os transtornos atuam alterando o humor. Apesar da terapia convencional oferecer um volume considerável de medicamentos ansiolíticos e antidepressivos, ao mesmo tempo, que novos estão sempre sendo desenvolvidos e testados, a aromaterapia surge como prática integrativa que pode ser empregada de forma alternativa ou complementar à medicina convencional. Aquela tem se revelado potencial, contribuindo com a mitigação do quadro de sintomas referentes à ansiedade e depressão. Assim, o presente trabalho tem por objetivo explanar, por meio de uma revisão integrativa, de que forma os óleos essenciais atuam no tratamento dos transtornos de ansiedade e depressão. O estudo se trata de uma revisão integrativa, constituída a partir de artigos que correspondem a estudos e ensaios clínicos publicados em periódicos entre 2018 e 2022. A análise é elaborada a partir de um total de 8 trabalhos selecionados. São estudos sobre a utilização dos óleos essenciais que apontam a aromaterapia como um recurso promissor no tratamento de transtornos mentais e comportamentais, graças à sua ação ansiolítica e antidepressiva, além de promover alivio aos sintomas decorrentes da ansiedade e da depressão. A aromaterapia pode ser uma favorável alternativa complementar ao tratamento medicamentoso da ansiedade e depressão, em virtude da sua ação ansiolítica e antidepressiva, oferecendo uma melhor qualidade de vida e recuperação da saúde dos pacientes.

Episodes involving behavioral disorders such as anxiety and depression have increased over the last decades. Both disorders act by altering mood. Although conventional therapy offers a considerable volume of anxiolytic and antidepressant drugs, at the same time that new ones are always being developed and tested, aromatherapy emerges as an integrative practice that can be used as an alternative or complement to conventional medicine. Aromatherapy has revealed its potential to contribute to the mitigation of symptoms related to anxiety and depression. Thus, the present work aims to explain, by means of an integrative review, how essential oils act in the treatment of anxiety and depression disorders. The study is an integrative review, consisting of articles corresponding to studies and clinical trials published in journals between 2018 and 2022. The analysis is elaborated from a total of 8 selected papers. These are studies on theuse of essential oils that point to aromatherapy as a promising resource in the treatment of mental and behavioral disorders, thanks to its anxiolytic and antidepressant action, in addition to promoting relief to symptoms arising from anxiety and depression. Aromatherapy may be a favorable complementary alternative to drug treatment for anxiety and depression, due to its anxiolytic and antidepressant action, offering a better quality of life and health recovery for patients.

Los episodios relacionados con trastornos del comportamiento como la ansiedad y la depresión han aumentado en las últimas décadas. Ambos trastornos actúan alterando el estado de ánimo. Aunque la terapia convencional ofrece un volumen considerable de fármacos ansiolíticos y antidepresivos, al mismo tiempo que siempre se están desarrollando y probando otros nuevos, la aromaterapia surge como una práctica integradora que puede utilizarse como alternativa o complemento a la medicina convencional. La aromaterapia ha revelado su potencial para contribuir a la mitigación de los síntomas relacionados conla ansiedad y la depresión. Así, el presente trabajo pretende explicar, mediante una revisión integradora, cómo actúan los aceites esenciales en el tratamiento de los trastornos de ansiedad y depresión. El estudio es una revisión integradora, compuesta por artículos correspondientes a estudios y ensayos clínicos publicados en revistas entre 2018 y 2022. El análisis se elabora a partir de un total de 8 artículos seleccionados. Se trata de estudios sobre el uso de aceites esenciales que señalan a la aromaterapia como un recurso prometedor en el tratamiento de trastornos mentales y del comportamiento, gracias a su acción ansiolítica y antidepresiva, además de favorecer el alivio de los síntomas derivados de la ansiedad y la depresión. La aromaterapia puede seruna alternativa complementaria favorable al tratamiento farmacológico de la ansiedad y la depresión, debido a su acción ansiolítica y antidepresiva, ofreciendo una mejor calidad de vida y recuperación de la salud de los pacientes.