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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-02-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC6383948?pdf=render |
| _version_ | 1828402239127945216 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T09:57:53Z |
| format | Article |
| id | doaj.art-8cc5ddaa83b043e2aaad8dbc1ec31ea7 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-10T09:57:53Z |
| publishDate | 2019-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-8cc5ddaa83b043e2aaad8dbc1ec31ea72022-12-22T01:53:26ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352019-02-01132e000712910.1371/journal.pntd.0007129Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents.Dana M KlugRosario Diaz-GonzalezGuiomar Pérez-MorenoGloria Ceballos-PérezRaquel García-HernándezVeronica Gomez-PérezLuis Miguel Ruiz-PérezDomingo I Rojas-BarrosFrancisco GamarroDolores González-PacanowskaMaría S Martínez-MartínezPilar ManzanoLori FerrinsConor R CaffreyMiguel NavarroMichael P PollastriNew 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.http://europepmc.org/articles/PMC6383948?pdf=render |
| spellingShingle | 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. PLoS Neglected Tropical Diseases |
| title | 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_short | 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 |
| url | http://europepmc.org/articles/PMC6383948?pdf=render |
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