title: Thiaplakortones A-D: antimalarial thiazine alkaloids from the Australian marine sponge Plakortis lita.
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 μM). Thiaplakortone A (1) was the most active natural product, with IC50 values of 51 and 6.6 nM against 3D7 and Dd2 lines, respectively.
authors.affiliation: Eskitis Institute, Griffith University , Nathan, Queensland 4111, Australia.
authors.forename: Rohan A
authors.initials: RA
authors.lastname: Davis
authors.forename: Sandra
authors.initials: S
authors.lastname: Duffy
authors.forename: Sabine
authors.initials: S
authors.lastname: Fletcher
authors.forename: Vicky M
authors.initials: VM
authors.lastname: Avery
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D001315:Australia; D001688:Biological Products; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D047229:Plakortis; D010963:Plasmodium falciparum / Q000187:drug effects; D011161:Porifera / Q000737:chemistry / Q000187:drug effects; D013843:Thiazines / Q000737:chemistry*; D014227:Triazines / Q000737:chemistry* / Q000494:pharmacology*; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D000962:Antimalarials; D001688:Biological Products; D013843:Thiazines; D014227:Triazines; C000589395:thiaplakortone A; D014364:Tryptophan