Structure-Activity Studies of Truncated Latrunculin Analogues with Antimalarial Activity
Swapna Varghese, Raphael Rahmani, Damien R Drew, James G Beeson, Jake Baum, Brian J Smith, Jonathan B Baell
ChemMedChem | WILEY-V C H VERLAG GMBH | Published : 2020
Malarial parasites employ actin dynamics for motility, and any disruption to these dynamics renders the parasites unable to effectively establish infection. Therefore, actin presents a potential target for malarial drug discovery, and naturally occurring actin inhibitors such as latrunculins are a promising starting point. However, the limited availability of the natural product and the laborious route for synthesis of latrunculins have hindered their potential development as drug candidates. In this regard, we recently described novel truncated latrunculins, with superior actin binding potency and selectivity towards P. falciparum actin than the canonical latrunculin B. In this paper, we fu..View full abstract
Awarded by Wellcome
Awarded by NHMRC
S.V. was supported by an Australian Government Research Training Program (RTP) scholarship. J.G.B. was supported by a Senior Research Fellowship and Program Grant from the National Health and Medical Research Council of Australia (NHMRC). The Burnet Institute is supported by the Victorian State Government Operational Infrastructure scheme and the NHMRC Independent Research Institutes Infrastructure Support scheme. J.B. was supported by an Investigator Award from Wellcome (100993/Z/13/Z). J.B.B. was supported by the NHMRC for Senior Research Fellowship APP1020411 and Principal Research Fellowship APP1117602. Australian Translational Medicinal Chemistry Facility (ATMCF) acknowledges the support of the Australian Government's National Collaborative Research Infrastructure Strategy (NCRIS) program via Therapeutic Innovation Australia (TIA).