دورية أكاديمية
Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infection.
| العنوان: | Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infection. |
|---|---|
| المؤلفون: | Cascabulho CM; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Inovações em Terapias, Ensino e Bioprodutos, Rio de Janeiro, RJ, Brasil., Meuser-Batista M; Fundação Oswaldo Cruz-Fiocruz, Instituto Fernandes Figueira, Departamento de Anatomia Patológica e Citopatologia, Laboratório de Patologia Molecular, Rio de Janeiro, RJ, Brasil., Moura KCG; Universidade Federal do Rio de Janeiro, Instituto de Pesquisa em Produtos Naturais, Rio de Janeiro, RJ, Brasil., Pinto MDC; Universidade Federal do Rio de Janeiro, Instituto de Pesquisa em Produtos Naturais, Rio de Janeiro, RJ, Brasil., Duque TLA; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Celular, Rio de Janeiro, RJ, Brasil., Demarque KC; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Celular, Rio de Janeiro, RJ, Brasil., Guimarães ACR; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Genômica Funcional e Bioinformática, Rio de Janeiro, RJ, Brasil., Manso PPA; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Patologia, Rio de Janeiro, RJ, Brasil., Pelajo-Machado M; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Patologia, Rio de Janeiro, RJ, Brasil., Oliveira GM; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Celular, Rio de Janeiro, RJ, Brasil., Castro SL; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Celular, Rio de Janeiro, RJ, Brasil., Menna-Barreto RF; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Celular, Rio de Janeiro, RJ, Brasil. |
| المصدر: | Memorias do Instituto Oswaldo Cruz [Mem Inst Oswaldo Cruz] 2020 Feb 14; Vol. 115, pp. e190389. Date of Electronic Publication: 2020 Feb 14 (Print Publication: 2020). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Instituto Oswaldo Cruz Country of Publication: Brazil NLM ID: 7502619 Publication Model: eCollection Cited Medium: Internet ISSN: 1678-8060 (Electronic) Linking ISSN: 00740276 NLM ISO Abbreviation: Mem Inst Oswaldo Cruz Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Rio de Janeiro : Instituto Oswaldo Cruz |
| مواضيع طبية MeSH: | Chagas Disease/*drug therapy , Naphthoquinones/*therapeutic use , Nitroimidazoles/*therapeutic use , Trypanocidal Agents/*therapeutic use, Acute Disease ; Animals ; Anti-Inflammatory Agents ; Disease Models, Animal ; Electrocardiography ; Male ; Mice ; Naphthoquinones/chemistry ; Nitroimidazoles/chemistry ; Parasitemia/drug therapy ; Time Factors ; Trypanocidal Agents/chemistry |
| مستخلص: | Background: Chagas disease, which is caused by the protozoan Trypanosoma cruzi, is endemic to Latin America and mainly affects low-income populations. Chemotherapy is based on two nitrocompounds, but their reduced efficacy encourages the continuous search for alternative drugs. Our group has characterised the trypanocidal effect of naphthoquinones and their derivatives, with naphthoimidazoles derived from β-lapachone (N1, N2 and N3) being the most active in vitro. Objectives: In the present work, the effects of N1, N2 and N3 on acutely infected mice were investigated. Methods: in vivo activity of the compounds was assessed by parasitological, biochemical, histopathological, immunophenotypical, electrocardiographic (ECG) and behavioral analyses. Findings: Naphthoimidazoles led to a decrease in parasitaemia (8 dpi) by reducing the number of bloodstream trypomastigotes by 25-50% but not by reducing mortality. N1 protected mice from heart injury (15 dpi) by decreasing inflammation. Bradycardia was also partially reversed after treatment with N1 and N2. Furthermore, the three compounds did not reverse hepatic and renal lesions or promote the improvement of other evaluated parameters. Main Conclusion: N1 showed moderate trypanocidal and promising immunomodulatory activities, and its use in combination with benznidazole and/or anti-arrhythmic drugs as well as the efficacy of its alternative formulations must be investigated in the near future. |
| References: | Mem Inst Oswaldo Cruz. 2012 Mar;107(2):211-6. (PMID: 22415260) Eur J Med Chem. 2004 Jul;39(7):639-45. (PMID: 15236845) PLoS Negl Trop Dis. 2016 Aug 23;10(8):e0004951. (PMID: 27551855) PLoS Pathog. 2012;8(4):e1002645. (PMID: 22532799) Mem Inst Oswaldo Cruz. 2010 Mar;105(2):233-8. (PMID: 20428688) Arzneimittelforschung. 2000 Dec;50(12):1120-8. (PMID: 11190779) Free Radic Biol Med. 2019 Jan;130:408-418. (PMID: 30445126) Wkly Epidemiol Rec. 2015 Feb 6;90(6):33-43. (PMID: 25671846) Molecules. 2009 Nov 10;14(11):4570-90. (PMID: 19924086) J Parasitol. 2016 Apr;102(2):280-5. (PMID: 26741817) N Engl J Med. 2015 Oct;373(14):1295-306. (PMID: 26323937) Microb Pathog. 2018 Jan;114:409-413. (PMID: 29233780) Curr Top Med Chem. 2016;16(20):2266-89. (PMID: 27072716) Antimicrob Agents Chemother. 2016 Jun 20;60(7):4297-309. (PMID: 27161638) Trans R Soc Trop Med Hyg. 1987;81(5):755-9. (PMID: 3130683) Am J Cardiovasc Drugs. 2015 Dec;15(6):387-93. (PMID: 26239259) ACS Chem Biol. 2018 Aug 17;13(8):1950-1957. (PMID: 29878754) J Proteomics. 2010 Nov 10;73(12):2306-15. (PMID: 20621210) Am J Physiol. 1998 Mar;274(3):H747-51. (PMID: 9530184) Arzneimittelforschung. 1997 Jan;47(1):74-9. (PMID: 9037448) Ann Trop Med Parasitol. 1978 Dec;72(6):523-31. (PMID: 367298) Mem Inst Oswaldo Cruz. 2009 Dec;104(8):1063-71. (PMID: 20140366) Expert Rev Anti Infect Ther. 2019 Sep;17(9):673-675. (PMID: 31361163) Sci Rep. 2017 Mar 03;7:42717. (PMID: 28256516) J Antimicrob Chemother. 2005 Dec;56(6):1034-41. (PMID: 16269551) Expert Opin Ther Pat. 2017 Oct;27(10):1111-1121. (PMID: 28586252) Parasitol Res. 2007 Sep;101(4):895-905. (PMID: 17546464) Rev Inst Med Trop Sao Paulo. 1962 Nov-Dec;4:389-96. (PMID: 14015230) J Chem Inf Comput Sci. 2004 May-Jun;44(3):1000-5. (PMID: 15154768) Curr Opin Infect Dis. 2018 Oct;31(5):415-421. (PMID: 30095485) Mem Inst Oswaldo Cruz. 2011 Sep;106(6):641-5. (PMID: 22012216) |
| المشرفين على المادة: | 0 (Anti-Inflammatory Agents) 0 (Naphthoquinones) 0 (Nitroimidazoles) 0 (Trypanocidal Agents) 6N4FA2QQ6A (beta-lapachone) YC42NRJ1ZD (benzonidazole) |
| تواريخ الأحداث: | Date Created: 20200220 Date Completed: 20200319 Latest Revision: 20220718 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC7029714 |
| DOI: | 10.1590/0074-02760190389 |
| PMID: | 32074167 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1678-8060 |
|---|---|
| DOI: | 10.1590/0074-02760190389 |