Polyamine diamide orthidine F as a potent and selective antimalarial lead compound

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dc.contributor.author Liew, Lydia en
dc.contributor.author Kaiser, M en
dc.contributor.author Copp, B en
dc.coverage.spatial Hotel Hesperia, La Toja, Spain en
dc.date.accessioned 2016-06-02T02:48:57Z en
dc.date.issued 2013 en
dc.identifier.citation 14th International Symposium on Marine Natural Products. 2013 en
dc.identifier.uri http://hdl.handle.net/2292/28972 en
dc.description.abstract THE POLYAMINE DIAMIDE ORTHIDINE F AS A POTENT AND SELECTIVE ANTIMALARIAL LEAD COMPOUND Orthidine F (1) was isolated from an extract of the marine organism Aplidium orthium, found at Three Kings Islands, New Zealand.1 An initial screen of the natural product 1 against a panel of parasitic protozoa (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum K1 dual drug-resistant strain) identified selective inhibitory activity for T. brucei rhodesiense (IC50 78 μM) against T. cruzi, no detectable activity towards L. donovani and moderate activity against P. falciparum. Furthermore, the natural product was found to be non-toxic in the non-malignant L6 rat myoblast cell line, thus representing an attractive target as an antiparasitic drug. A preliminary structure-activity relationship (SAR) study identified analogues with a similar activity profile to the natural product. The analogues were found to exhibit moderate inhibitory activity against T. brucei rhodesiense (IC50 3.2–210 μM), more potent inhibitory activity against P. falciparum (IC50 0.0086–0.61 μM), and no significant activity against T. cruzi and L. donovani. The analogues also continued to display little or no cytotoxic effect in the L6 cell line, this combined with the potent IC50 values obtained for inhibition of P. falciparum afforded a series of analogues with impressive properties which warranted further studies. This led to a second series of analogues with the intention of improving its antimalarial activity. The analogues generated from this exercise exhibited potent in vitro activities (IC50 0.0086–0.61 μM) while retaining selectivity against P. falciparum. Three analogues were selected based on the in vitro data obtained and evaluated for in vivo activity in the Plasmodium berghei mouse model of malaria; which in this instance did not yield significant activity. en
dc.description.uri http://www.manapro2013.com/ en
dc.relation.ispartof 14th International Symposium on Marine Natural Products en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Polyamine diamide orthidine F as a potent and selective antimalarial lead compound en
dc.type Conference Poster en
pubs.author-url http://www.manapro2013.com/Gesconet/uploads/ficheros/17/ABSTRACTS%20MaNaPro%20part%202.pdf en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.elements-id 416022 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Auckland Cancer Research en
pubs.record-created-at-source-date 2013-12-06 en

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