Magnificines A and B, Antimicrobial Marine Alkaloids Featuring a Tetrahydrooxazolo[3,2-a]azepine-2,5(3H,6H)-dione Backbone from the Red Sea Sponge Negombata magnifica

Abstract

Investigation of the Red Sea sponge Negombata magnifica gave two novel alkaloids, magnificines A and B (1 and 2) and a new β-ionone derivative, (±)-negombaionone (3), together with the known latrunculin B (4) and 16-epi-latrunculin B (5). The analysis of the NMR and HRESIMS spectra supported the planar structures and the relative configurations of the compounds. The absolute configurations of magnificines A and B were determined by the analysis of the predicted and experimental ECD spectra. Magnificines A and B possess a previously unreported tetrahydrooxazolo[3,2-a]azepine-2,5(3H,6H)-dione backbone and represent the first natural compounds in this class. (±)-Negombaionone is the first β-ionone of a sponge origin. Compounds 1-3 displayed selective activity against Escherichia coli in a disk diffusion assay with inhibition zones up to 22 mm at a concentration of 50 µg/disc and with MIC values down to 8.0 µM. Latrunculin B and 16-epi-latrunculin B inhibited the growth of HeLa cells with IC50 values down to 1.4 µM.

DU8ML: Machine Learning-Augmented Density Functional Theory Nuclear Magnetic Resonance Computations for High-Throughput In Silico Solution Structure Validation and Revision of Complex Alkaloids

“…Magnificines A and B, alkaloids containing hydroperoxy-oxazolidinone moiety, have been recently isolated from the Red Sea sponge Negombata magnifica (Figure ). However, the DU8ML calculated spectra showed irreconcilable differences with the reported NMR data.…”

Hemimycalins C–E; Cytotoxic and Antimicrobial Alkaloids with Hydantoin and 2-Iminoimidazolidin-4-one Backbones from the Red Sea Marine Sponge Hemimycale sp.

“…The compounds reduced the growth of orthotopic tumors and repressed the formation of tumor micrometastases in distant organs without apparent cytotoxic effects at the test doses [18]. As a continuation of our work to uncover biologically active alkaloids from marine organisms [19][20][21][22], the cytotoxic fractions of a methanolic extract of the sponge Hemimycale species were investigated. Three new alkaloids, hemimycalins C-E (1-3) with hydantoin and 2-iminoimidazolidin-4-one backbones, were obtained from the active fractions of the extract, and their structures were characterized.…”

Marine natural products

“…471,472 A Negombata sponge yielded nor-triterpenoid 1160; other structures were claimed but are inconsistent with the spectroscopic data provided and are not shown here. 473 A series of nortetraterpenoids 1161-1164 were isolated from a Vietnamese Clathria. 474 The rst total synthesis of various plakorsin and ancorinoside lipids have been reported, 475,476 as has the synthesis of polyketide peroxides muqubilin and several negombatoperoxides.…”

“…471,472 A Negombata sponge yielded nor-triterpenoid 1160 ; other structures were claimed but are inconsistent with the spectroscopic data provided and are not shown here. 473 A series of nor-tetraterpenoids 1161–1164 were isolated from a Vietnamese Clathria . 474…”