Psammaplysin H, a new antimalarial bromotyrosine alkaloid from a marine sponge of the genus Pseudoceratina

Abstract

Mass-directed isolation of the CH(2)Cl(2)/CH(3)OH extract from a marine sponge of the genus Pseudoceratina resulted in the purification of a new antimalarial bromotyrosine alkaloid, psammaplysin H (1), along with the previously isolated analogs psammaplysins G (2) and F (3). The structure of 1 was elucidated following 1D and 2D NMR, and MS data analysis. All compounds were tested in vitro against the 3D7 line of Plasmodium falciparum and mammalian cell lines (HEK293 and HepG2), with 1 having the most potent (IC(50) 0.41μM) and selective (>97-fold) antimalarial activity.

Twilight Zone Sponges from Guam Yield Theonellin Isocyanate and Psammaplysins I and J

“…On examining minimised structures of 5 with 6 R *, 7 R * and 6 R *, 7 S * configurations it was evident that the 6 R *, 7 R * configured molecule would be the one expected to show no NOE interactions between H 2 -5 and H-7. This information, combined with comparable specific rotation data as well as comparable 13 C NMR chemical shifts for C-5, C-6 and C-7 and 1 H NMR shifts for H 2 -5 and H-7 to that of the other psammaplysins 14, 18-22 indicated 5 and 6 to have the same relative configurations as the ones previously reported. Based on our data it was not possible to make deductions concerning the configuration of C-19 in 6 .…”

“…The two proton resonances at δ 3.09 and 3.42 (C H 2 -5) displayed a large 16.0 Hz coupling, similar to that found in the 4,5-dihydro-1,2-oxazole moiety of fistularins 16, 17 and in the 4,6-dibromo-5-methoxy-2,3-dihydrooxepine moiety of psammaplysins. 14, 18-22 Closer inspection of the 13 C NMR data of 5 clearly showed it was characteristic of a psammaplysin skeleton rather than a fistularin, particularly the characteristic resonance for the spiro-carbon C-6 (121.7 ppm). In fact, the C-1 to C-12 part of 5 was found to be identical to that of psammaplysins A ( 7 ) 14 and F. 20 The molecular formula of 5 indicated it differed from 7 by having one less bromine atom in the phenyl ring and from psammaplysin F by missing the same bromine as well as the methyl of the N -CH 3 group.…”

“…Upon completion of the planar structure analysis of 5 and 6 , their relative configurations required assignment. Literature research revealed that stereochemical assignments for psammaplysins reported to date, A-H, 14, 18-22 were based on data comparisons made with psammaplysin A whose relative configuration was determined by single crystal X-ray crystallographic analysis. 14 In the 2D NOESY data of 5 it was apparent that there were no interactions between either of the protons attached to C-5 and H-7.…”

“…Previously reported biological activity data for psammaplysins 14, 18-22 and the fact that poly-brominated compounds are unlikely to ever be progressed further than preliminary laboratory screening efforts due to their instability, no further biological evaluations of our materials were undertaken.…”

Antiparasitic Bromotyrosine Derivatives from the Marine Sponge Verongula rigida

“…For this reason, bromotyrosine metabolites have been considered as potential chemotaxonomic markers of Verongida sponges [9,10]. A wide range of biological activities has been reported for some of these secondary metabolites, including antimicrobial, anti-enzymatic, cytotoxic and antiparasitic activities [11–13]. Previous studies on the sponge V. rigida led to the discovery of antimicrobial and enzymatic activity of its extracts [14,15] and the isolation and structure identification of bromotyrosine-derived compounds [8,16,17].…”