New 1,2,3-triazole-based analogues of benznidazole for use against Trypanosoma cruzi infection : In vitro and in vivo evaluations
© 2018 John Wiley & Sons A/S..
Chagas disease has spread throughout the world mainly because of the migration of infected individuals. In Brazil, only benznidazole (Bnz) is used; however, it is toxic and not active in the chronic phase, and cases of resistance are described. This work aimed at the synthesis and the trypanocidal evaluation in vitro and in vivo of six new Bnz analogues (3-8). They were designed by exploring the bioisosteric substitution between the amide group contained in Bnz and the 1,2,3-triazole ring. All the compounds were synthesized in good yields. With the exception of compound 7, the in vitro biological evaluation shows that all Bnz analogues were active against the amastigote form, whereas only compounds 3, 4, 5, and 8 were active against trypomastigote. Compounds 4 and 5 showed the most promising activities in vitro against the form of trypomastigote, being more active than Bnz. In vivo evaluation of compounds, 3-8 showed lower potency and higher toxicity than Bnz. Although the 1,2,3-triazole ring has been described in the literature as an amide bioisostere, its substitution here has reduced the activity of the compounds and made them more toxic. Thus, further molecular optimization could provide novel therapeutic agents for Chagas' disease.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:92 |
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| Enthalten in: |
Chemical biology & drug design - 92(2018), 3 vom: 09. Sept., Seite 1670-1682 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Leite, Débora Inácio [VerfasserIn] |
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| Links: |
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| Themen: |
1,2,3-triazoles |
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| Anmerkungen: |
Date Completed 31.07.2019 Date Revised 31.07.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/cbdd.13333 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM283919167 |
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| 245 | 1 | 0 | |a New 1,2,3-triazole-based analogues of benznidazole for use against Trypanosoma cruzi infection |b In vitro and in vivo evaluations |
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| 520 | |a © 2018 John Wiley & Sons A/S. | ||
| 520 | |a Chagas disease has spread throughout the world mainly because of the migration of infected individuals. In Brazil, only benznidazole (Bnz) is used; however, it is toxic and not active in the chronic phase, and cases of resistance are described. This work aimed at the synthesis and the trypanocidal evaluation in vitro and in vivo of six new Bnz analogues (3-8). They were designed by exploring the bioisosteric substitution between the amide group contained in Bnz and the 1,2,3-triazole ring. All the compounds were synthesized in good yields. With the exception of compound 7, the in vitro biological evaluation shows that all Bnz analogues were active against the amastigote form, whereas only compounds 3, 4, 5, and 8 were active against trypomastigote. Compounds 4 and 5 showed the most promising activities in vitro against the form of trypomastigote, being more active than Bnz. In vivo evaluation of compounds, 3-8 showed lower potency and higher toxicity than Bnz. Although the 1,2,3-triazole ring has been described in the literature as an amide bioisostere, its substitution here has reduced the activity of the compounds and made them more toxic. Thus, further molecular optimization could provide novel therapeutic agents for Chagas' disease | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a 1,2,3-triazoles | |
| 650 | 4 | |a 2-nitroimidazole | |
| 650 | 4 | |a benznidazole | |
| 650 | 4 | |a click chemistry | |
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| 700 | 1 | |a Bastos, Monica Macedo |e verfasserin |4 aut | |
| 700 | 1 | |a Hoelz, Lucas Villas Boas |e verfasserin |4 aut | |
| 700 | 1 | |a Bianco, Maria da Conceição Avelino Dias |e verfasserin |4 aut | |
| 700 | 1 | |a de Oliveira, Andressa Paula |e verfasserin |4 aut | |
| 700 | 1 | |a da Silva, Patricia Bernardino |e verfasserin |4 aut | |
| 700 | 1 | |a da Silva, Cristiane França |e verfasserin |4 aut | |
| 700 | 1 | |a Batista, Denise da Gama Jean |e verfasserin |4 aut | |
| 700 | 1 | |a da Gama, Aline Nefertiti Silva |e verfasserin |4 aut | |
| 700 | 1 | |a Peres, Raiza Brandão |e verfasserin |4 aut | |
| 700 | 1 | |a Villar, Jose Daniel Figueroa |e verfasserin |4 aut | |
| 700 | 1 | |a Soeiro, Maria de Nazaré Correia |e verfasserin |4 aut | |
| 700 | 1 | |a Boechat, Nubia |e verfasserin |4 aut | |
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