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

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.

Marine natural products

“…435 Tedaniophorbasins A 1020 and B 1021 are inherently uorescent alkaloids from Tedaniophorbas ceratosis. 436 The rst thiazide-containing NP, neopetrothiazide 1022 has been reported from Neopetrosia sp. collected from Palau.…”

Structural and Biological Insights into the Hot‐Spot Marine Natural Products Reported from 2012 to 2021

“…[ 175 ] Tedaniophorbasin A ( 190 ), from a sponge Tedaniophorbas ceratosis, is a highly fluorescent pteridine alkaloid possessing a novel skeleton with a thiomorpholine motif. [ 176 ]…”

Structure Revision of Formyl Phloroglucinol Meroterpenoids: A Unified Approach Using NMR Fingerprinting and DFT NMR and ECD Analyses

“…Unfortunately, with incorrectly assigned NP structures continuing to pollute the literature and associated large NP databases, the accuracy of AI-based computational analyses for aiding NP structure elucidation will likely be compromised. While less computationally expensive NMR fact-checking methods are emerging [3,24], solution state GIAO DFT calculations remain best practice for accurately assessing the connectivity and configuration of NP structures [25][26][27]. In addition, comparative metrics commonly employed to compare the accuracy of DFT NMR-calculated chemical shifts with experimental ones, specifically MAE and RMSD, can be expanded upon with DP4+ Bayesian theorem algorithms [28,29].…”