Tedaniophorbasins A and B-Novel Fluorescent Pteridine Alkaloids Incorporating a Thiomorpholine from the Sponge Tedaniophorbas ceratosis.

Asadhawut Hiranrat,Wilawan Mahabusarakam,John N A Hooper,Darren C Holland,Anthony R Carroll,Vicky M Avery

doi:10.3390/md19020095

Asadhawut Hiranrat, Wilawan Mahabusarakam + Show 4 more

Open Access

https://doi.org/10.3390/md19020095

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Abstract

Two new fluorescent pteridine alkaloids, tedaniophorbasins A (1) and B (2), together with the known alkaloid N-methyltryptamine, were isolated, through application of mass directed purification, from the sponge Tedaniophorbas ceratosis collected from northern New South Wales, Australia. The structures of tedaniophorbasins A and B were deduced from the analysis of 1D/2D NMR and MS data and through application of 13C NMR DFT calculations. Tedaniophorbasin A possesses a novel 2-imino-1,3-dimethyl-2,3,7,8-tetrahydro-1H-[1,4]thiazino[3,2-g]pteridin-4(6H)-one skeleton, while tedaniophorbasin B is its 2-oxo derivative. The compounds show significant Stokes shifts (~14,000 cm−1) between excitation and emission wavelengths in their fluorescence spectra. The new compounds were tested for bioactivity against chloroquine-sensitive and chloroquine-resistant strains of the malaria parasite Plasmodium falciparum, breast and pancreatic cancer cell lines, and the protozoan parasite Trypanosoma brucei brucei but were inactive against all targets at 40 µM.

Highlights

The frozen sponge was chopped into ceratosis
The frozen sponge was chopped into small cation in MeOH
Marine pteridine alkaloids have previously been isolated from polychaete w sponges [15], ascidians [14,19], and fungi [20]

Summary

Results and Discussion sponge

The frozen sponge was chopped into ceratosis. small pieces and extracted by repeated sonication in MeOH. The extract-impregnated gel was separated by preparative HPLC on C18 -bonded silica gel with a gradient from 1% aqueous TFA to MeOH containing 1% TFA with one min. 175 and 265, fractions 19 and 20 had an ion peak at m/z 175 and fraction 27 had an ion peak at m/z 266 These fractions were evaporated and analyzed by 1 H NMR spectroscopy. Fractions 17 and 18 contained a mixture of 1 and N-methyltryptamine. These compounds were separated from each other by recrystallization from MeOH. The IR spectrum of 1 had absorption bands at 1712 and 1679 cm−1 , suggesting that it contained amide and aromatic groups. Edited HSQC correlations (Figure S5) indicated that two of the proton singlets could be assigned to N-methyl groups δH/C 3.66/31.3 and 3.46/30.3 and two were methylene groups δH/C 3.65/40.6 and 3.34/26.3, while the remaining two signals were due

Results and Discussion

Marine pteridine to tedaniophorbasins

General Chemistry Experimental Procedures

DFT 13 C NMR Calculations

Biological Activity Testing

Conclusions