In Vitro Pharmacological and Toxicological Effects of Norterpene Peroxides Isolated from the Red Sea Sponge Diacarnus erythraeanus on Normal and Cancer Cells

Abstract

Eight cyclic peroxide norterpenoids, compounds 1-8, have been isolated and characterized from the Red Sea sponge Diacarnus erythraeanus, including two new norsesterterpene derivatives (3, 4). Among these metabolites, (-)-muqubilin A (5) (nine cell lines analyzed) and the new compounds 3 and 4 (seven cell lines analyzed) displayed mean IC₅₀ growth inhibitory concentrations in vitro of <10 μM, while the remaining compounds (1, 6-8) were inactive in these cancer cell lines. Compound 5 displayed no selectivity between normal and cancer cells in terms of in vitro growth inhibition. Quantitative video microscopy analysis carried out on (-)-muqubilin A-treated cells validated the data obtained by means of the MTT colorimetric assay, while flow cytometry analysis revealed ROS production but no induction of apoptosis in cancer cells.

New Metabolites from the South China Sea Sponge <i>Diacarnus megaspinorhabdosa</i>

“…The E-geometry of this double bond was deduced from the carbon chemical shift of the C10-methyl (δ C 16.0, C-18) 7,17) and the NOESY correlation between H-9 (δ H 2.18) and H-11 (δ H 5.07) (Fig. 2).…”

“…3,9-11) Recently, attention has been drawn on these metabolites because of their pharmaceutical properties, including antimalarial, 8,12) antimicrobial, 12) Trypanosoma brucei inhibitory, 13) sea urchin egg cell-division inhibitory, 14) cytotoxic, 4,7,15) antiulcer and antihypotensive activities.…”

“…1) Sponges of genus Diacarnus are recognized as being prolific sources to produce terpene peroxides and related derivatives, which include norterpene ketones, dienes, diols and other types of compounds. [2][3][4][5][6][7][8] From a biosynthetic perspective, the biosynthetic origin of some or all marine norterpene cyclic peroxides involved a common intermediate C6 hydroperoxide, undergoing a "Michael addition" to an adjacent α,β-unsaturated carboxylic acid or ester moiety. 6) As an offshoot of the biosynthetic pathway, the norterpene ketones can be derived from the hydroperoxide carboxylic aid precursor by oxidative degradation.…”

“…6) Such ketones are increasingly being identified as minor co-metabolites with norterpene cyclic peroxides. 3,[9][10][11] Recently, attention has been drawn on these metabolites because of their pharmaceutical properties, including antimalarial, 8,12) antimicrobial, 12) Trypanosoma brucei inhibitory, 13) sea urchin egg cell-division inhibitory, 14) cytotoxic, 4,7,15) antiulcer and antihypotensive activities. 16) As our previous chemical research on the sponge D. megaspinorhabdosa, five norterpene cyclic peroxides diacarperoxides H-L have been isolated.…”

DeepScreen: An Accurate, Rapid, and Anti‐Interference Screening Approach for Nanoformulated Medication by Deep Learning

“…We notice that machine learning has been extensively used in medical research and gain some progress 9, 10. Recent researches demonstrate that machine learning could identify some indiscoverable change of cells and predict their variation tendency or process 11, 12. Machine learning approaches could distinguish the slight change of treated cells in the earlier stage of drug function and realizing a self‐acting evaluation without much intervention from subjective action.…”