Tandem Synthesis of Furanaphthoquinones via Enamines and Evaluation of Their Antiparasitic Effects against Trypanosoma cruzi
Furanaphthoquinones are well known in medicinal chemistry for exhibiting relevant structural heterogeneity and bioactivities. In this work, it was synthesized a series of furanaphthoquinones through a tandem reaction between lawsone (8) and cyclic ketones in the presence of morpholine. This strategy provides an efficient and general method for synthesizing furanaphthoquinones with activity against the epimastigote form of Trypanosoma cruzi (T. cruzi), the parasite that causes Chagas disease. Compound 9b was the better prototype, and it exhibited high potency for causing parasite death, showed reduced acute toxicity towards mammalian cells, and was capable of rupturing the epimastigote plasma membrane and acting on sterol 14α-demethylase (CYP51). Additionally, 9b reduced trypomastigote viability by 99% after 24 h. Candidate 9b demonstrated the best and most promising profile when bound to CYP51.
Main Authors: | , , , , , , , , |
---|---|
Format: | Digital revista |
Language: | English |
Published: |
Sociedade Brasileira de Química
2022
|
Online Access: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532022000300238 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
id |
oai:scielo:S0103-50532022000300238 |
---|---|
record_format |
ojs |
spelling |
oai:scielo:S0103-505320220003002382022-02-18Tandem Synthesis of Furanaphthoquinones via Enamines and Evaluation of Their Antiparasitic Effects against Trypanosoma cruziCardoso,Mariana F. CForezi,Luana S. MSouza,Acácio S. deFaria,Ana F. MGalvão,Raissa M. SBello,Murilo LSilva,Fernando C. daFaria,Robson XFerreira,Vitor F quinones lawsone lapachones Chagas disease neglected diseases Furanaphthoquinones are well known in medicinal chemistry for exhibiting relevant structural heterogeneity and bioactivities. In this work, it was synthesized a series of furanaphthoquinones through a tandem reaction between lawsone (8) and cyclic ketones in the presence of morpholine. This strategy provides an efficient and general method for synthesizing furanaphthoquinones with activity against the epimastigote form of Trypanosoma cruzi (T. cruzi), the parasite that causes Chagas disease. Compound 9b was the better prototype, and it exhibited high potency for causing parasite death, showed reduced acute toxicity towards mammalian cells, and was capable of rupturing the epimastigote plasma membrane and acting on sterol 14α-demethylase (CYP51). Additionally, 9b reduced trypomastigote viability by 99% after 24 h. Candidate 9b demonstrated the best and most promising profile when bound to CYP51.info:eu-repo/semantics/openAccessSociedade Brasileira de QuímicaJournal of the Brazilian Chemical Society v.33 n.3 20222022-03-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532022000300238en10.21577/0103-5053.20210142 |
institution |
SCIELO |
collection |
OJS |
country |
Brasil |
countrycode |
BR |
component |
Revista |
access |
En linea |
databasecode |
rev-scielo-br |
tag |
revista |
region |
America del Sur |
libraryname |
SciELO |
language |
English |
format |
Digital |
author |
Cardoso,Mariana F. C Forezi,Luana S. M Souza,Acácio S. de Faria,Ana F. M Galvão,Raissa M. S Bello,Murilo L Silva,Fernando C. da Faria,Robson X Ferreira,Vitor F |
spellingShingle |
Cardoso,Mariana F. C Forezi,Luana S. M Souza,Acácio S. de Faria,Ana F. M Galvão,Raissa M. S Bello,Murilo L Silva,Fernando C. da Faria,Robson X Ferreira,Vitor F Tandem Synthesis of Furanaphthoquinones via Enamines and Evaluation of Their Antiparasitic Effects against Trypanosoma cruzi |
author_facet |
Cardoso,Mariana F. C Forezi,Luana S. M Souza,Acácio S. de Faria,Ana F. M Galvão,Raissa M. S Bello,Murilo L Silva,Fernando C. da Faria,Robson X Ferreira,Vitor F |
author_sort |
Cardoso,Mariana F. C |
title |
Tandem Synthesis of Furanaphthoquinones via Enamines and Evaluation of Their Antiparasitic Effects against Trypanosoma cruzi |
title_short |
Tandem Synthesis of Furanaphthoquinones via Enamines and Evaluation of Their Antiparasitic Effects against Trypanosoma cruzi |
title_full |
Tandem Synthesis of Furanaphthoquinones via Enamines and Evaluation of Their Antiparasitic Effects against Trypanosoma cruzi |
title_fullStr |
Tandem Synthesis of Furanaphthoquinones via Enamines and Evaluation of Their Antiparasitic Effects against Trypanosoma cruzi |
title_full_unstemmed |
Tandem Synthesis of Furanaphthoquinones via Enamines and Evaluation of Their Antiparasitic Effects against Trypanosoma cruzi |
title_sort |
tandem synthesis of furanaphthoquinones via enamines and evaluation of their antiparasitic effects against trypanosoma cruzi |
description |
Furanaphthoquinones are well known in medicinal chemistry for exhibiting relevant structural heterogeneity and bioactivities. In this work, it was synthesized a series of furanaphthoquinones through a tandem reaction between lawsone (8) and cyclic ketones in the presence of morpholine. This strategy provides an efficient and general method for synthesizing furanaphthoquinones with activity against the epimastigote form of Trypanosoma cruzi (T. cruzi), the parasite that causes Chagas disease. Compound 9b was the better prototype, and it exhibited high potency for causing parasite death, showed reduced acute toxicity towards mammalian cells, and was capable of rupturing the epimastigote plasma membrane and acting on sterol 14α-demethylase (CYP51). Additionally, 9b reduced trypomastigote viability by 99% after 24 h. Candidate 9b demonstrated the best and most promising profile when bound to CYP51. |
publisher |
Sociedade Brasileira de Química |
publishDate |
2022 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532022000300238 |
work_keys_str_mv |
AT cardosomarianafc tandemsynthesisoffuranaphthoquinonesviaenaminesandevaluationoftheirantiparasiticeffectsagainsttrypanosomacruzi AT foreziluanasm tandemsynthesisoffuranaphthoquinonesviaenaminesandevaluationoftheirantiparasiticeffectsagainsttrypanosomacruzi AT souzaacaciosde tandemsynthesisoffuranaphthoquinonesviaenaminesandevaluationoftheirantiparasiticeffectsagainsttrypanosomacruzi AT fariaanafm tandemsynthesisoffuranaphthoquinonesviaenaminesandevaluationoftheirantiparasiticeffectsagainsttrypanosomacruzi AT galvaoraissams tandemsynthesisoffuranaphthoquinonesviaenaminesandevaluationoftheirantiparasiticeffectsagainsttrypanosomacruzi AT bellomurilol tandemsynthesisoffuranaphthoquinonesviaenaminesandevaluationoftheirantiparasiticeffectsagainsttrypanosomacruzi AT silvafernandocda tandemsynthesisoffuranaphthoquinonesviaenaminesandevaluationoftheirantiparasiticeffectsagainsttrypanosomacruzi AT fariarobsonx tandemsynthesisoffuranaphthoquinonesviaenaminesandevaluationoftheirantiparasiticeffectsagainsttrypanosomacruzi AT ferreiravitorf tandemsynthesisoffuranaphthoquinonesviaenaminesandevaluationoftheirantiparasiticeffectsagainsttrypanosomacruzi |
_version_ |
1756403860415447040 |