BibTex format
@article{Delves:2018:10.1038/s41467-018-05777-2,
author = {Delves, M and Miguel-Blanco, C and Matthews, H and Molina, I and Ruecker, A and Yahiya, S and Straschil, U and Abraham, M and Leon-Diaz, ML and Fischer, O and Zubiaurre, A and Brandt, J and Cortes, A and Barnard, A and Fuchter, M and Calderon, F and Winzeler, E and Sinden, R and Herreros, E and Gamo, FJ and Baum, J},
doi = {10.1038/s41467-018-05777-2},
journal = {Nature Communications},
title = {A high throughput screen for next-generation leads targeting malaria parasite transmission},
url = {http://dx.doi.org/10.1038/s41467-018-05777-2},
volume = {9},
year = {2018}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Spread of parasite resistance to artemisinin threatens current frontline antimalarial therapies, highlighting the need for new drugs with alternative modes of action. Since only 0.2–1% of asexual parasites differentiate into sexual, transmission-competent forms, targeting this natural bottleneck provides a tangible route to interrupt disease transmission and mitigate resistance selection. Here we present a high-throughput screen of gametogenesis against a ~70,000 compound diversity library, identifying seventeen drug-like molecules that target transmission. Hit molecules possess varied activity profiles including male-specific, dual acting male–female and dual-asexual-sexual, with one promising N-((4-hydroxychroman-4-yl)methyl)-sulphonamide scaffold found to have sub-micromolar activity in vitro and in vivo efficacy. Development of leads with modes of action focussed on the sexual stages of malaria parasite development provide a previously unexplored base from which future therapeutics can be developed, capable of preventing parasite transmission through the population.
AU - Delves,M
AU - Miguel-Blanco,C
AU - Matthews,H
AU - Molina,I
AU - Ruecker,A
AU - Yahiya,S
AU - Straschil,U
AU - Abraham,M
AU - Leon-Diaz,ML
AU - Fischer,O
AU - Zubiaurre,A
AU - Brandt,J
AU - Cortes,A
AU - Barnard,A
AU - Fuchter,M
AU - Calderon,F
AU - Winzeler,E
AU - Sinden,R
AU - Herreros,E
AU - Gamo,FJ
AU - Baum,J
DO - 10.1038/s41467-018-05777-2
PY - 2018///
SN - 2041-1723
TI - A high throughput screen for next-generation leads targeting malaria parasite transmission
T2 - Nature Communications
UR - http://dx.doi.org/10.1038/s41467-018-05777-2
UR - http://hdl.handle.net/10044/1/62850
VL - 9
ER -