29886-63-3Relevant articles and documents
Truncated Latrunculins as Actin Inhibitors Targeting Plasmodium falciparum Motility and Host Cell Invasion
Johnson, Swapna,Rahmani, Rapha?l,Drew, Damien R.,Williams, Melanie J.,Wilkinson, Mark,Tan, Yan Hong,Huang, Johnny X.,Tonkin, Christopher J.,Beeson, James G.,Baum, Jake,Smith, Brian J.,Baell, Jonathan B.
, p. 10994 - 11005 (2016/12/30)
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 synthesized 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 that of latrunculin B against P. 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.
The stille cross coupling reactions on solid support. Link to solution phase directed ortho metalation. An ester linker approach to styryl, biaryl and heterobiaryl carboxylic acids
Chamoin, Sylvie,Houldsworth, Stephen,Snieckus, Victor
, p. 4175 - 4178 (2007/10/03)
The synthesis of the titled compounds by Stille cross coupling on Merrifield resin - linked halo benzoates with stannanes followed by LiOH hydrolysis is reported.
