Muito além do praziquantel: uma revisão sobre o reposicionamento de fármacos contra esquistossomose nos últimos 10 anos
Data
2023-12-07
Autores
Castro, Renato Ferreira de 
Orientadores
Santos, Katia Cristina Pereira Oliveira
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A esquistossomose é uma doença parasitária causada por Schistosoma spp. Possui alta morbidade, pois causa falência hepática na forma intestinal, e hematúria e infertilidade na forma urogenital. O praziquantel é atualmente o tratamento de escolha da doença, entretanto seu uso massivo gera preocupação sobre o surgimento de cepas resistentes. O reposicionamento de fármacos é uma abordagem promissora na busca de novos fármacos anti-parasitários, pois reduz o tempo e custos de pesquisa. Neste trabalho foram revisados 48 artigos que descreveram o uso de 123 fármacos em testes in sílico, in vitro, in vivo, e ensaios clínicos como candidatos ao seu reposicionamento no combate da esquistossomose no período entre 2013 e 2023. Das classes de fármacos utilizados nos testes de reposicionamento os antitumorais, fármacos com ação no sistema cardiovascular, antimicrobianos e antimaláricos tiveram maior número de representantes e destaque. A maior parte dos fármacos foi testada apenas in vitro na espécie S. mansoni, nas fases de vermes adultos e esquistossômulos. Nos estudos realizados in vivo, a maioria dos fármacos foi administrada na fase patente da doença, por via oral. A miltefosina foi o fármaco mais testado nesta última década; entretanto os fármacos mais eficientes testados in vivo com base nas taxas de redução da carga de vermes e de ovos em administrações em fase pré-patente da infecção foram a artemisinina combinada com naftoquina fosfato e citrato de tamoxifeno, respectivamente. Já a prometazina foi o fármaco mais eficiente administrado na fase patente (maiores taxas de redução da carga de vermes e de ovos), sendo este um candidato interessante a ser utilizado no combate desta parasitose. Destacamos a importância de testar os fármacos reposicionados em outras espécies do gênero, além de S. mansoni, pois podem apresentar taxa de eficácia variável. Esta revisão da literatura reforça que o reposicionamento de fármacos é uma estratégia útil na busca de novos fármacos no combate da esquistossomose, porém deve ser realizada com cautela e não deve ser a única estratégia usada para este fim.
Schistosomiasis is a parasitic disease caused by Schistosoma spp. It has high morbidity, as it causes liver failure in the intestinal form, and hematuria and infertility in the urogenital form. Praziquantel is currently the treatment of choice for the disease; however its massive use raises concerns about the emergence of resistant strains. Drug repurposing is a promising approach in the search for new anti parasitic drugs, as it reduces research time and costs. In this work, 48 articles were reviewed that described the use of 123 drugs in in silico, in vitro, in vivo tests, and clinical trials as candidates for their repurposing in the fight against schistosomiasis in the period between 2013 and 2023. Of the classes of drugs used in the tests of repositioning antitumor drugs, drugs that act on the cardiovascular system, antimicrobials and antimalarials had a greater number of representatives and prominence. Most of the drugs were tested only in vitro on the species S. mansoni, in the adult worm and schistosomula stages. In in vivo studies, most drugs were administered orally during the patent phase of the disease. Miltefosine was the most tested drug in the last decade; however, the most efficient drugs tested in vivo based on the Worm burden r eduction and egg burden reduction in administrations in the pre patent phase of infection were artemisinin combined with naphthoquine phosphate and tamoxifen citrate, respectively. Promethazine was the most efficient drug administered in the patent phase (highest worm burden reduction and egg burden reduction ), making it an interesting candidate to be used in the treatment of this parasitosis. We highlight the importance of testing repositioned drugs in other species of the genus, in addition to S. mansoni, as they may have a variable efficacy rate. This literature review reinforces that drug repurposing is a useful strategy in the search for new drugs to combat schistosomiasis, but it must be carried out with caution and should not be the only strategy used for this goal.
Schistosomiasis is a parasitic disease caused by Schistosoma spp. It has high morbidity, as it causes liver failure in the intestinal form, and hematuria and infertility in the urogenital form. Praziquantel is currently the treatment of choice for the disease; however its massive use raises concerns about the emergence of resistant strains. Drug repurposing is a promising approach in the search for new anti parasitic drugs, as it reduces research time and costs. In this work, 48 articles were reviewed that described the use of 123 drugs in in silico, in vitro, in vivo tests, and clinical trials as candidates for their repurposing in the fight against schistosomiasis in the period between 2013 and 2023. Of the classes of drugs used in the tests of repositioning antitumor drugs, drugs that act on the cardiovascular system, antimicrobials and antimalarials had a greater number of representatives and prominence. Most of the drugs were tested only in vitro on the species S. mansoni, in the adult worm and schistosomula stages. In in vivo studies, most drugs were administered orally during the patent phase of the disease. Miltefosine was the most tested drug in the last decade; however, the most efficient drugs tested in vivo based on the Worm burden r eduction and egg burden reduction in administrations in the pre patent phase of infection were artemisinin combined with naphthoquine phosphate and tamoxifen citrate, respectively. Promethazine was the most efficient drug administered in the patent phase (highest worm burden reduction and egg burden reduction ), making it an interesting candidate to be used in the treatment of this parasitosis. We highlight the importance of testing repositioned drugs in other species of the genus, in addition to S. mansoni, as they may have a variable efficacy rate. This literature review reinforces that drug repurposing is a useful strategy in the search for new drugs to combat schistosomiasis, but it must be carried out with caution and should not be the only strategy used for this goal.