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Efficacy of sertraline against Trypanosoma cruzi : an in vitro and in silico study.

التفاصيل البيبلوغرافية
العنوان: Efficacy of sertraline against Trypanosoma cruzi : an in vitro and in silico study.
المؤلفون: Ferreira DD; Instituto Adolfo Lutz, Centre for Parasitology and Mycology, Avenida Dr. Arnaldo 351, 8° andar, sala 9, CEP, São Paulo, SP 01246-000 Brazil., Mesquita JT; Instituto Adolfo Lutz, Centre for Parasitology and Mycology, Avenida Dr. Arnaldo 351, 8° andar, sala 9, CEP, São Paulo, SP 01246-000 Brazil., da Costa Silva TA; Instituto Adolfo Lutz, Centre for Parasitology and Mycology, Avenida Dr. Arnaldo 351, 8° andar, sala 9, CEP, São Paulo, SP 01246-000 Brazil., Romanelli MM; Instituto Adolfo Lutz, Centre for Parasitology and Mycology, Avenida Dr. Arnaldo 351, 8° andar, sala 9, CEP, São Paulo, SP 01246-000 Brazil., da Gama Jaen Batista D; 2Fundação Oswaldo Cruz, Laboratório de Biologia Celular do Instituto Oswaldo Cruz, Av. Brasil, 4365 Manguinhos, CEP, Rio de Janeiro, RJ 21040-360 Brazil., da Silva CF; 2Fundação Oswaldo Cruz, Laboratório de Biologia Celular do Instituto Oswaldo Cruz, Av. Brasil, 4365 Manguinhos, CEP, Rio de Janeiro, RJ 21040-360 Brazil., da Gama ANS; 2Fundação Oswaldo Cruz, Laboratório de Biologia Celular do Instituto Oswaldo Cruz, Av. Brasil, 4365 Manguinhos, CEP, Rio de Janeiro, RJ 21040-360 Brazil., Neves BJ; 3Faculdade de Farmácia, Universidade Federal de Goiás, Rua 240 Setor Leste Universitário, Goiânia, GO 74605170 Brazil., Melo-Filho CC; 3Faculdade de Farmácia, Universidade Federal de Goiás, Rua 240 Setor Leste Universitário, Goiânia, GO 74605170 Brazil., Correia Soeiro MN; 2Fundação Oswaldo Cruz, Laboratório de Biologia Celular do Instituto Oswaldo Cruz, Av. Brasil, 4365 Manguinhos, CEP, Rio de Janeiro, RJ 21040-360 Brazil., Andrade CH; 3Faculdade de Farmácia, Universidade Federal de Goiás, Rua 240 Setor Leste Universitário, Goiânia, GO 74605170 Brazil., Tempone AG; Instituto Adolfo Lutz, Centre for Parasitology and Mycology, Avenida Dr. Arnaldo 351, 8° andar, sala 9, CEP, São Paulo, SP 01246-000 Brazil.
المصدر: The journal of venomous animals and toxins including tropical diseases [J Venom Anim Toxins Incl Trop Dis] 2018 Oct 30; Vol. 24, pp. 30. Date of Electronic Publication: 2018 Oct 30 (Print Publication: 2018).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: CEVAP Country of Publication: Brazil NLM ID: 101201501 Publication Model: eCollection Cited Medium: Print ISSN: 1678-9199 (Print) Linking ISSN: 16789180 NLM ISO Abbreviation: J Venom Anim Toxins Incl Trop Dis Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: 2019- : Botucatu, SP, Brazil : CEVAP
Original Publication: Botucatu, SP, Brazil : CEVAP, c2003-
مستخلص: Background: Drug repurposing has been an interesting and cost-effective approach, especially for neglected diseases, such as Chagas disease.
Methods: In this work, we studied the activity of the antidepressant drug sertraline against Trypanosoma cruzi trypomastigotes and intracellular amastigotes of the Y and Tulahuen strains, and investigated its action mode using cell biology and in silico approaches.
Results: Sertraline demonstrated in vitro efficacy against intracellular amastigotes of both T. cruzi strains inside different host cells, including cardiomyocytes, with IC 50 values between 1 to 10 μM, and activity against bloodstream trypomastigotes, with IC 50 of 14 μM. Considering the mammalian cytotoxicity, the drug resulted in a selectivity index of 17.8. Sertraline induced a change in the mitochondrial integrity of T. cruzi , resulting in a decrease in ATP levels, but not affecting reactive oxygen levels or plasma membrane permeability. In silico approaches using chemogenomic target fishing, homology modeling and molecular docking suggested the enzyme isocitrate dehydrogenase 2 of T. cruzi ( Tc IDH2) as a potential target for sertraline.
Conclusions: The present study demonstrated that sertraline had a lethal effect on different forms and strains of T. cruzi , by affecting the bioenergetic metabolism of the parasite. These findings provide a starting point for future experimental assays and may contribute to the development of new compounds.
Competing Interests: Animal procedures were performed with the approval of the Research Ethics Commission, in agreement with the Guidelines for the Care and Use of Laboratory Animals from the National Academy of Sciences. All procedures carried out at Institute Adolfo Lutz were approved by the Committee for Ethics in the Use of Animals (CEUA 04/2016). All procedures performed at Fiocruz were in accordance with the guidelines established by the Fiocruz Committee for Ethics in the Use of Animals (CEUA LW16/14).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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فهرسة مساهمة: Keywords: Drug; Drug repositioning; Drug repurposing; Sertraline; Treatment; Trypanosoma cruzi
تواريخ الأحداث: Date Created: 20181120 Latest Revision: 20220330
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6208092
DOI: 10.1186/s40409-018-0165-8
PMID: 30450114
قاعدة البيانات: MEDLINE
الوصف
تدمد:1678-9199
DOI:10.1186/s40409-018-0165-8