Synthesis and structure-activity relationship study of pyrrolidine-oxadiazoles as anthelmintics against Haemonchus contortus
Copyright © 2020 Elsevier Masson SAS. All rights reserved..
Parasitic roundworms (nematodes) are significant pathogens of humans and animals and cause substantive socioeconomic losses due to the diseases that they cause. The control of nematodes in livestock animals relies heavily on the use of anthelmintic drugs. However, their extensive use has led to a widespread problem of drug resistance in these worms. Thus, the discovery and development of novel chemical entities for the treatment of parasitic worms of humans and animals is needed. Herein, we describe our medicinal chemistry optimization efforts of a phenotypic hit against Haemonchus contortus based on a pyrrolidine-oxadiazole scaffold. This led to the identification of compounds with potent inhibitory activities (IC50 = 0.78-22.4 μM) on the motility and development of parasitic stages of H. contortus, and which were found to be highly selective in a mammalian cell counter-screen. These compounds could be used as suitable chemical tools for drug target identification or as lead compounds for further optimization.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:190 |
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| Enthalten in: |
European journal of medicinal chemistry - 190(2020) vom: 15. März, Seite 112100 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ruan, Banfeng [VerfasserIn] |
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| Links: |
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| Themen: |
Anthelmintic |
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| Anmerkungen: |
Date Completed 04.12.2020 Date Revised 14.12.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejmech.2020.112100 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM306135140 |
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| 500 | |a Date Revised 14.12.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a Parasitic roundworms (nematodes) are significant pathogens of humans and animals and cause substantive socioeconomic losses due to the diseases that they cause. The control of nematodes in livestock animals relies heavily on the use of anthelmintic drugs. However, their extensive use has led to a widespread problem of drug resistance in these worms. Thus, the discovery and development of novel chemical entities for the treatment of parasitic worms of humans and animals is needed. Herein, we describe our medicinal chemistry optimization efforts of a phenotypic hit against Haemonchus contortus based on a pyrrolidine-oxadiazole scaffold. This led to the identification of compounds with potent inhibitory activities (IC50 = 0.78-22.4 μM) on the motility and development of parasitic stages of H. contortus, and which were found to be highly selective in a mammalian cell counter-screen. These compounds could be used as suitable chemical tools for drug target identification or as lead compounds for further optimization | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Anthelmintic | |
| 650 | 4 | |a Drug discovery | |
| 650 | 4 | |a Haemonchus contortus | |
| 650 | 4 | |a Pyrrolidine-oxadiazoles | |
| 650 | 4 | |a Structure-activity relationship | |
| 650 | 7 | |a Anthelmintics |2 NLM | |
| 650 | 7 | |a Oxadiazoles |2 NLM | |
| 650 | 7 | |a Pyrrolidines |2 NLM | |
| 700 | 1 | |a Zhang, Yuezhou |e verfasserin |4 aut | |
| 700 | 1 | |a Tadesse, Solomon |e verfasserin |4 aut | |
| 700 | 1 | |a Preston, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Taki, Aya C |e verfasserin |4 aut | |
| 700 | 1 | |a Jabbar, Abdul |e verfasserin |4 aut | |
| 700 | 1 | |a Hofmann, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Jiao, Yaqing |e verfasserin |4 aut | |
| 700 | 1 | |a Garcia-Bustos, Jose |e verfasserin |4 aut | |
| 700 | 1 | |a Harjani, Jitendra |e verfasserin |4 aut | |
| 700 | 1 | |a Le, Thuy Giang |e verfasserin |4 aut | |
| 700 | 1 | |a Varghese, Swapna |e verfasserin |4 aut | |
| 700 | 1 | |a Teguh, Silvia |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Yiyue |e verfasserin |4 aut | |
| 700 | 1 | |a Odiba, Jephthah |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Gasser, Robin B |e verfasserin |4 aut | |
| 700 | 1 | |a Baell, Jonathan |e verfasserin |4 aut | |
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