BibTex format
@article{Johnson:2016:10.1021/acs.jmedchem.6b01109,
author = {Johnson, S and Rahmani, R and Drew, DR and Williams, MJ and Huang, JX and Tan, YH and Wilkinson, M and Tonkin, CJ and Beeson, JG and Baum, J and Smith, BJ and Baell, J},
doi = {10.1021/acs.jmedchem.6b01109},
journal = {Journal of Medicinal Chemistry},
pages = {10994--11005},
title = {Truncated latrunculins as actin inhibitors targeting plasmodium falciparum motility and host-cell invasion},
url = {http://dx.doi.org/10.1021/acs.jmedchem.6b01109},
volume = {59},
year = {2016}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Polymerization of the cytosolic protein actin is critical to cell movement and host-cell invasion by the malaria parasite, Plasmodium falciparum. Any disruption to actin polymerization dynamics will render the parasite incapable of invading a host cell and thereby unable to cause infection. Here, we explore the potential of using truncated latrunculins as potential chemotherapeutics for the treatment of malaria. Exploration of the binding interactions of the natural actin inhibitor latrunculins, with actin revealed how a truncated core of the inhibitor could retain its key interaction features with actin. This truncated core was synthesised and subjected to preliminary structure-activity relationship studies to generate a focused set of analogues. Biochemical analyses of these analogues demonstrate their 6-fold increased activity compared with latrunculin B against Plasmodium falciparum and a 16-fold improved selectivity ex vivo. These data establish the latrunculin core as a potential focus for future structure-based drug design of chemotherapeutics against malaria.
AU - Johnson,S
AU - Rahmani,R
AU - Drew,DR
AU - Williams,MJ
AU - Huang,JX
AU - Tan,YH
AU - Wilkinson,M
AU - Tonkin,CJ
AU - Beeson,JG
AU - Baum,J
AU - Smith,BJ
AU - Baell,J
DO - 10.1021/acs.jmedchem.6b01109
EP - 11005
PY - 2016///
SN - 0022-2623
SP - 10994
TI - Truncated latrunculins as actin inhibitors targeting plasmodium falciparum motility and host-cell invasion
T2 - Journal of Medicinal Chemistry
UR - http://dx.doi.org/10.1021/acs.jmedchem.6b01109
UR - http://hdl.handle.net/10044/1/42492
VL - 59
ER -
