Thiaplakortones A-D: Antimalarial Thiazine Alkaloids from the Australian Marine Sponge Plakortis lita

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Davis, Rohan A
Duffy, Sandra
Fletcher, Sabine
Avery, Vicky M
Quinn, Ronald J
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2013
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Abstract

A high-throughput screening campaign using a prefractionated natural product library and an in vitro antimalarial assay identified active fractions derived from the Australian marine sponge Plakortis lita . Bioassay-guided fractionation of the CH2Cl2/CH3OH extract from P. lita resulted in the purification of four novel thiazine-derived alkaloids, thiaplakortones A-D (1-4). The chemical structures of 1-4 were determined following analysis of 1D/2D NMR and MS data. Comparison of the chiro-optical data for 3 and 4 with literature values of related N-methyltryptophan natural products was used to determine the absolute configuration for both thiaplakortones C and D as 11S. Compounds 1-4 displayed significant growth inhibition against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum (IC50 values <651 nM) and only moderate cytotoxicity against HEK293 cells (IC50 values >3.9 卩. Thiaplakortone A (1) was the most active natural product, with IC50 values of 51 and 6.6 nM against 3D7 and Dd2 lines, respectively.

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Journal of Organic Chemistry

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78

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19

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This document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of Organic Chemistry, copyright 2013 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/jo400988y

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Medicinal and biomolecular chemistry

Medicinal and biomolecular chemistry not elsewhere classified

Organic chemistry

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