Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents.
New treatments are needed for neglected tropical diseases (NTDs) such as Human African trypanosomiasis (HAT), Chagas disease, and schistosomiasis. Through a whole organism high-throughput screening campaign, we previously identified 797 human kinase inhibitors that grouped into 59 structural cluster...
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Online Access: | https://doi.org/10.1371/journal.pntd.0007129 https://doaj.org/article/8cc5ddaa83b043e2aaad8dbc1ec31ea7 |
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ftdoajarticles:oai:doaj.org/article:8cc5ddaa83b043e2aaad8dbc1ec31ea7 2023-05-15T15:01:27+02:00 Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents. Dana M Klug Rosario Diaz-Gonzalez Guiomar Pérez-Moreno Gloria Ceballos-Pérez Raquel García-Hernández Veronica Gomez-Pérez Luis Miguel Ruiz-Pérez Domingo I Rojas-Barros Francisco Gamarro Dolores González-Pacanowska María S Martínez-Martínez Pilar Manzano Lori Ferrins Conor R Caffrey Miguel Navarro Michael P Pollastri 2019-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0007129 https://doaj.org/article/8cc5ddaa83b043e2aaad8dbc1ec31ea7 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC6383948?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007129 https://doaj.org/article/8cc5ddaa83b043e2aaad8dbc1ec31ea7 PLoS Neglected Tropical Diseases, Vol 13, Iss 2, p e0007129 (2019) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2019 ftdoajarticles https://doi.org/10.1371/journal.pntd.0007129 2022-12-31T00:23:26Z New treatments are needed for neglected tropical diseases (NTDs) such as Human African trypanosomiasis (HAT), Chagas disease, and schistosomiasis. Through a whole organism high-throughput screening campaign, we previously identified 797 human kinase inhibitors that grouped into 59 structural clusters and showed activity against T. brucei, the causative agent of HAT. We herein report the results of further investigation of one of these clusters consisting of substituted isatin derivatives, focusing on establishing structure-activity and -property relationship scope. We also describe their in vitro absorption, distribution, metabolism, and excretion (ADME) properties. For one isatin, NEU-4391, which offered the best activity-property profile, pharmacokinetic parameters were measured in mice. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 13 2 e0007129 |
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Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Dana M Klug Rosario Diaz-Gonzalez Guiomar Pérez-Moreno Gloria Ceballos-Pérez Raquel García-Hernández Veronica Gomez-Pérez Luis Miguel Ruiz-Pérez Domingo I Rojas-Barros Francisco Gamarro Dolores González-Pacanowska María S Martínez-Martínez Pilar Manzano Lori Ferrins Conor R Caffrey Miguel Navarro Michael P Pollastri Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
New treatments are needed for neglected tropical diseases (NTDs) such as Human African trypanosomiasis (HAT), Chagas disease, and schistosomiasis. Through a whole organism high-throughput screening campaign, we previously identified 797 human kinase inhibitors that grouped into 59 structural clusters and showed activity against T. brucei, the causative agent of HAT. We herein report the results of further investigation of one of these clusters consisting of substituted isatin derivatives, focusing on establishing structure-activity and -property relationship scope. We also describe their in vitro absorption, distribution, metabolism, and excretion (ADME) properties. For one isatin, NEU-4391, which offered the best activity-property profile, pharmacokinetic parameters were measured in mice. |
format |
Article in Journal/Newspaper |
author |
Dana M Klug Rosario Diaz-Gonzalez Guiomar Pérez-Moreno Gloria Ceballos-Pérez Raquel García-Hernández Veronica Gomez-Pérez Luis Miguel Ruiz-Pérez Domingo I Rojas-Barros Francisco Gamarro Dolores González-Pacanowska María S Martínez-Martínez Pilar Manzano Lori Ferrins Conor R Caffrey Miguel Navarro Michael P Pollastri |
author_facet |
Dana M Klug Rosario Diaz-Gonzalez Guiomar Pérez-Moreno Gloria Ceballos-Pérez Raquel García-Hernández Veronica Gomez-Pérez Luis Miguel Ruiz-Pérez Domingo I Rojas-Barros Francisco Gamarro Dolores González-Pacanowska María S Martínez-Martínez Pilar Manzano Lori Ferrins Conor R Caffrey Miguel Navarro Michael P Pollastri |
author_sort |
Dana M Klug |
title |
Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents. |
title_short |
Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents. |
title_full |
Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents. |
title_fullStr |
Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents. |
title_full_unstemmed |
Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents. |
title_sort |
evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-sleeping sickness agents. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2019 |
url |
https://doi.org/10.1371/journal.pntd.0007129 https://doaj.org/article/8cc5ddaa83b043e2aaad8dbc1ec31ea7 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 13, Iss 2, p e0007129 (2019) |
op_relation |
http://europepmc.org/articles/PMC6383948?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007129 https://doaj.org/article/8cc5ddaa83b043e2aaad8dbc1ec31ea7 |
op_doi |
https://doi.org/10.1371/journal.pntd.0007129 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
13 |
container_issue |
2 |
container_start_page |
e0007129 |
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1766333477881380864 |