Journal article
Hundreds of dual-stage antimalarial molecules discovered by a functional gametocyte screen
- Abstract:
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Plasmodium falciparum stage V gametocytes are responsible for parasite transmission, and drugs targeting this stage are needed to support malaria elimination. We here screen the Tres Cantos Antimalarial Set (TCAMS) using the previously developed P. falciparum female gametocyte activation assay (Pf FGAA), which assesses stage V female gametocyte viability and functionality using Pfs25 expression. We identify over 400 compounds with activities <2μM, chemically classified into 57 clusters and 33 singletons. Up to 68% of the hits are chemotypes described for the first time as late-stage gametocyte-targeting molecules. In addition, the biological profile of 90 compounds representing the chemical diversity is assessed. We confirm in vitro transmission-blocking activity of four of the six selected molecules belonging to three distinct scaffold clusters. Overall, this TCAMS gametocyte screen provides 276 promising antimalarial molecules with dual asexual/sexual activity, representing starting points for target identification and candidate selection.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 787.1KB, Terms of use)
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- Publisher copy:
- 10.1038/ncomms15160
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 8
- Pages:
- 15160
- Publication date:
- 2017-03-03
- Acceptance date:
- 2017-05-17
- DOI:
- ISSN:
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2041-1723
- Language:
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English
- Keywords:
- Pubs id:
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pubs:696729
- UUID:
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uuid:ebc33149-ebf8-4484-813e-d2649947ce90
- Local pid:
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pubs:696729
- Source identifiers:
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696729
- Deposit date:
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2017-05-26
Terms of use
- Copyright holder:
- Miguel-Blanco et al
- Copyright date:
- 2017
- Notes:
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Copyright The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0
International License. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise
in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material.
To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
- Licence:
- CC Attribution (CC BY)
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