Open Source Drug Discovery: Highly Potent Antimalarial Compounds Derived from the Tres Cantos Arylpyrroles

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Author(s)
Williamson, Alice E
Ylioja, Paul M
Robertson, Murray N
Antonova-Koch, Yevgeniya
Avery, Vicky
Baell, Jonathan B
Batchu, Harikrishna
Batra, Sanjay
Burrows, Jeremy N
Bhattacharyya, Soumya
Calderon, Felix
Charman, Susan A
Clark, Julie
Crespo, Benigno
Dean, Matin
Debbert, Stefan L
Delves, Michael
Dennis, Adelaide SM
Deroose, Frederik
Duffy, Sandra
Fletcher, Sabine
Giaever, Guri
Hallyburton, Irene
Gamo, Francisco-Javier
Gebbia, Marinella
Guy, R Kiplin
Hungerford, Zoe
Kirk, Kiaran
Lafuente-Monasterio, Maria J
Lee, Anna
Meister, Stephan
Nislow, Corey
Overington, John P
Papadatos, George
Patiny, Luc
Pham, James
Ralph, Stuart A
Ruecker, Andrea
Ryan, Eileen
Southan, Christopher
Srivastava, Kumkum
Swain, Chris
Tarnowski, Matthew J
Thomson, Patrick
Turner, Peter
Wallace, Iain M
Wells, Timothy NC
White, Karen
White, Laura
Willis, Paul
Winzeler, Elizabeth A
Wittlin, Sergio
Todd, Matthew H
Year published
2016
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Show full item recordAbstract
The development of new antimalarial compounds remains a pivotal part of the strategy for malaria elimination. Recent large-scale phenotypic screens have provided a wealth of potential starting points for hit-to-lead campaigns. One such public set is explored, employing an open source research mechanism in which all data and ideas were shared in real time, anyone was able to participate, and patents were not sought. One chemical subseries was found to exhibit oral activity but contained a labile ester that could not be replaced without loss of activity, and the original hit exhibited remarkable sensitivity to minor structural ...
View more >The development of new antimalarial compounds remains a pivotal part of the strategy for malaria elimination. Recent large-scale phenotypic screens have provided a wealth of potential starting points for hit-to-lead campaigns. One such public set is explored, employing an open source research mechanism in which all data and ideas were shared in real time, anyone was able to participate, and patents were not sought. One chemical subseries was found to exhibit oral activity but contained a labile ester that could not be replaced without loss of activity, and the original hit exhibited remarkable sensitivity to minor structural change. A second subseries displayed high potency, including activity within gametocyte and liver stage assays, but at the cost of low solubility. As an open source research project, unexplored avenues are clearly identified and may be explored further by the community; new findings may be cumulatively added to the present work.
View less >
View more >The development of new antimalarial compounds remains a pivotal part of the strategy for malaria elimination. Recent large-scale phenotypic screens have provided a wealth of potential starting points for hit-to-lead campaigns. One such public set is explored, employing an open source research mechanism in which all data and ideas were shared in real time, anyone was able to participate, and patents were not sought. One chemical subseries was found to exhibit oral activity but contained a labile ester that could not be replaced without loss of activity, and the original hit exhibited remarkable sensitivity to minor structural change. A second subseries displayed high potency, including activity within gametocyte and liver stage assays, but at the cost of low solubility. As an open source research project, unexplored avenues are clearly identified and may be explored further by the community; new findings may be cumulatively added to the present work.
View less >
Journal Title
ACS Central Science
Volume
2
Issue
10
Copyright Statement
© 2016 The Authors. This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Subject
Chemical sciences
Pharmacology and pharmaceutical sciences not elsewhere classified