Theoretical and experimental studies of new modified isoflavonoids as potential inhibitors of topoisomerase I from Plasmodium falciparum.

DNA topoisomerase I from Plasmodium falciparum (PfTopoI), a potential selective target for chemotherapy and drug development against malaria, is used here, together with human Topo I (HssTopoI), for docking, molecular dynamics (MD) studies and experimental assays. Six synthetic isoflavonoid derivati...

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Autores principales:	Wilian A Cortopassi, Julia Penna-Coutinho, Anna C C Aguiar, André S Pimentel, Camilla D Buarque, Paulo R R Costa, Bruna R M Alves, Tanos C C França, Antoniana U Krettli
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fdfc16d0a2f848da92672d1df059ed90
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spelling	oai:doaj.org-article:fdfc16d0a2f848da92672d1df059ed902021-11-18T08:27:11ZTheoretical and experimental studies of new modified isoflavonoids as potential inhibitors of topoisomerase I from Plasmodium falciparum.1932-620310.1371/journal.pone.0091191https://doaj.org/article/fdfc16d0a2f848da92672d1df059ed902014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24651068/?tool=EBIhttps://doaj.org/toc/1932-6203DNA topoisomerase I from Plasmodium falciparum (PfTopoI), a potential selective target for chemotherapy and drug development against malaria, is used here, together with human Topo I (HssTopoI), for docking, molecular dynamics (MD) studies and experimental assays. Six synthetic isoflavonoid derivatives and the known PfTopoI inhibitors camptothecin and topotecan were evaluated in parallel. Theoretical results suggest that these compounds dock in the binding site of camptothecin and topotecan inside both enzymes and that LQB223 binds selectively in PfTopoI. In vitro tests against P. falciparum blood parasites corroborated the theoretical findings. The selectivity index (SI) of LQB223 ≥ 98 suggests that this molecule is the most promising in the group of compounds tested. In vivo experiments in mice infected with P. berghei showed that LQB223 has an antimalarial activity similar to that of chloroquine.Wilian A CortopassiJulia Penna-CoutinhoAnna C C AguiarAndré S PimentelCamilla D BuarquePaulo R R CostaBruna R M AlvesTanos C C FrançaAntoniana U KrettliPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e91191 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wilian A Cortopassi Julia Penna-Coutinho Anna C C Aguiar André S Pimentel Camilla D Buarque Paulo R R Costa Bruna R M Alves Tanos C C França Antoniana U Krettli Theoretical and experimental studies of new modified isoflavonoids as potential inhibitors of topoisomerase I from Plasmodium falciparum.
description	DNA topoisomerase I from Plasmodium falciparum (PfTopoI), a potential selective target for chemotherapy and drug development against malaria, is used here, together with human Topo I (HssTopoI), for docking, molecular dynamics (MD) studies and experimental assays. Six synthetic isoflavonoid derivatives and the known PfTopoI inhibitors camptothecin and topotecan were evaluated in parallel. Theoretical results suggest that these compounds dock in the binding site of camptothecin and topotecan inside both enzymes and that LQB223 binds selectively in PfTopoI. In vitro tests against P. falciparum blood parasites corroborated the theoretical findings. The selectivity index (SI) of LQB223 ≥ 98 suggests that this molecule is the most promising in the group of compounds tested. In vivo experiments in mice infected with P. berghei showed that LQB223 has an antimalarial activity similar to that of chloroquine.
format	article
author	Wilian A Cortopassi Julia Penna-Coutinho Anna C C Aguiar André S Pimentel Camilla D Buarque Paulo R R Costa Bruna R M Alves Tanos C C França Antoniana U Krettli
author_facet	Wilian A Cortopassi Julia Penna-Coutinho Anna C C Aguiar André S Pimentel Camilla D Buarque Paulo R R Costa Bruna R M Alves Tanos C C França Antoniana U Krettli
author_sort	Wilian A Cortopassi
title	Theoretical and experimental studies of new modified isoflavonoids as potential inhibitors of topoisomerase I from Plasmodium falciparum.
title_short	Theoretical and experimental studies of new modified isoflavonoids as potential inhibitors of topoisomerase I from Plasmodium falciparum.
title_full	Theoretical and experimental studies of new modified isoflavonoids as potential inhibitors of topoisomerase I from Plasmodium falciparum.
title_fullStr	Theoretical and experimental studies of new modified isoflavonoids as potential inhibitors of topoisomerase I from Plasmodium falciparum.
title_full_unstemmed	Theoretical and experimental studies of new modified isoflavonoids as potential inhibitors of topoisomerase I from Plasmodium falciparum.
title_sort	theoretical and experimental studies of new modified isoflavonoids as potential inhibitors of topoisomerase i from plasmodium falciparum.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/fdfc16d0a2f848da92672d1df059ed90
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Theoretical and experimental studies of new modified isoflavonoids as potential inhibitors of topoisomerase I from Plasmodium falciparum.

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