The treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed, and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against Schistosoma mansoni ex vivo and in a murine model of schistosomiasis. In vitro assays demonstrated that promethazine affected parasite motility and viability, and it induced severe tegumental damage in schistosomes. The 50% lethal concentration (LC50) of the drug was 5.84 μM. Similar to promethazine, schistosomes incubated with atropine, a classical anticholinergic drug, displayed reduced motor activity. In an animal model, promethazine treatment was introduced at an oral dose of 100 mg/kg of body weight for five successive days at different intervals from the time of infection for the evaluation of the stage-specific susceptibility (prepatent and patent infections). Various parasitological criteria indicated the following in vivo antischistosomal effects of promethazine: there were significant reductions in worm burden, egg production, hepatomegaly, and splenomegaly. The highest worm burden reduction was achieved with promethazine in patent infections (>90%). Taken together, considering the importance of the repositioning of drugs in infectious diseases, especially those related to poverty, our data revealed the possibility of promethazine repositioning as an antischistosomal agent.
Praziquantel is the only available drug to treat schistosomiasis, a parasitic disease that currently infects more than 240 million people globally. Due to increasing concerns about resistance and inadequate efficacy there is a need for new therapeutics. In this study, a series of 17 pyrazolines (15–31) and three pyrazoles (32–34) were synthesized and evaluated for their antiparasitic properties against ex vivo adult Schistosoma mansoni worms. Of the 20 compounds tested, six had a 50% effective concentration (EC50) below 30 μM. Our best hit, pyrazoline 22, showed promising activity against adult schistosomes, with an EC50 < 10 µM. Additionally, compound 22 had low cytotoxicity, with selectivity index of 21.6 and 32.2 for monkey and human cell lines, respectively. All active pyrazolines demonstrated a negative effect on schistosome fecundity, with a marked reduction in the number of eggs. Structure–activity relationship analysis showed that the presence of the non-aromatic heterocycle and N-substitution are fundamental to the antischistosomal properties. Pharmacokinetics, drug-likeness and medicinal chemistry friendliness studies were performed, and predicted values demonstrated an excellent drug-likeness profile for pyrazolines as well as an adherence to major pharmaceutical companies’ filters. Collectively, this study demonstrates that pyrazoline derivatives are promising scaffolds in the discovery of novel antischistosomal agents.
O objetivo foi comparar o número de diagnóstico e óbito da hanseníase no Brasil no período de 2010 a 2020, considerando a pandemia de Covid-19, e assim analisar de que maneira este evento interferiu na sistemática de diagnóstico e óbito em pacientes com hanseníase. Estudo epidemiológico descritivo com abordagem quantitativa de dados secundários disponibilizados no DATASUS, que incluiu as informações de todas as notificações e óbitos entre indivíduos com hanseníase que tiveram no período citado, modo de entrada “caso novo”, nos estados do Brasil. Os resultados mostraram tendência de queda anual no número total de novos casos de hanseníase no país, com grande redução em 2020. Em relação ao número de óbitos, a região Nordeste foi a responsável pela maior parte dos óbitos em pacientes em acompanhamento na última década. A pandemia intensifica desafios e vulnerabilidades anteriores, sendo imperativo implementar políticas públicas de saúde voltadas à hanseníase.
Introdução: em 2020, o mundo foi marcado por uma crise: a pandemia COVID-19. A principal medida adotada para diminuição da contaminação é o isolamento social. Isso desencadeou diversas consequências nos âmbitos da saúde, nas esferas socioeconômicas, e, nas relações interpessoais, resultando em condições estressoras. Objetivo: analisar na literatura quais são as principais consequências do isolamento social na saúde mental da população durante a pandemia de COVID-19. Métodos: trata-se de uma revisão narrativa da literatura, de natureza qualitativa. Foi utilizado a estratégia PICO (acrônimo para patient, intervention, comparison, outcomes) para a elaboração da questão de pesquisa desta revisão. Resultados: encontrou-se que o isolamento social causa impacto na saúde mental de diversos grupos da sociedade, gerando incertezas, medo, ansiedade, perdas econômicas e sofrimento psíquico significativo, podendo levar a um desequilíbrio emocional e consequente adoecimento e morte pela COVID-19, como também repercutir na epidemia de transtornos mentais na população. Conclusão: o isolamento social imposto para a contenção da pandemia, intensifica desafios e vulnerabilidades anteriores, sendo importante implementar políticas públicas voltadas a saúde mental.
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