@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}
}

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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  - 

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