Dolabellane Diterpenoids from the Xisha Soft Coral Clavularia viridis

Abstract

Twelve new members (1–12) of the dolabellane family, co-occurring with three related known diterpenoids (13–15), were isolated from the Xisha soft coral Clavularia viridis. Their structures were determined by extensive spectroscopic analysis, modified Mosher’s method, and X-ray diffraction analysis. Clavuperoxylides A (3) and B (4) represent the first examples of dolabellanes containing peroxyl groups, especially the novel peroxide bridge in 4, whereas clavufuranolides A–C (9–11) are the first example of dolabellane diterpenoids comprising a tetrahydrofuran ring. The possible biogenetic relationship of all the isolates was proposed. In bioassay, several compounds exhibited considerable cytotoxicity against A549 and P388 cell lines. Compound 7 exhibited inhibitory activity against protein tyrosine phosphatases 1B (PTP1B), an anti-diabetic target, representing the first report of PTP1B inhibitory activity for dolabellane diterpenoids.

Targeted Isolation of Dolabellane Diterpenoids from the Soft Coral Clavularia viridis Using Molecular Networking

“…The molecular formula of clavirolide Q ( 8 ) was determined as C 20 H 30 O 2 with six degrees of unsaturation. The NMR data (Tables and ) featured a dolabellane-type diterpene, closely related to those of clavufuranolide C . The presence of six olefinic resonances for three double bonds along with the remaining carbons for sp 3 resonances suggested a tricyclic structure.…”

“…LC–MS/MS-based molecular networking provides an effective tool to distinguish the structure features from a metabolic profile. Among the developed strategies, the Global Natural Product Social Molecular Networking (GNPS) platform is widely used for the dereplication and recognition of target metabolites. − In the present work, LC–MS/MS-based molecular networking coupled to molecular annotation by the molecular networking workflow on the GNPS platform , was used to screen the coral species from the in-house coral library, and the soft coral Clavularia viridis was selected for further chemical examination because of the metabolite cluster annotated to dolabellane-related diterpenes (Figure ), of which clavirolides F ( m/z 333 [M + H] + ), B, D, E, I ( m/z 317 [M + H] + ), , C ( m/z 341 [M + Na] + ), and G ( m/z 301 [M + H] + ); clavularinlides A ( m/z 331 [M + H] + ) and B ( m/z 349 [M + H] + ); clavufuranolide C ( m/z 287 [M + H] + ); and clavinflols C ( m/z 395 [M + Na] + ) and A ( m/z 327 [M + Na] + ) were characterized. These dolabellane analogues were subsequently obtained by chromatographic separation, and their structures were identified by the spectroscopic data in comparison with those reported in the literature.…”

Methanol Extract of Clavularia inflata Exerts Apoptosis and DNA Damage to Oral Cancer Cells

“…C. viridis -derived 4-deacetoxyl-12- O -deacetylclavulone I showed an IC 50 value of 2.5 μg/mL for prostate cancer cells (PC3) based on a sulforhodamine B assay at 48 h [ 17 ]. C. viridis -derived clavuperoxylides B showed an IC 50 value of 5.23 μg/mL for lung cancer cells (A549) based on a CCK-8 assay at 72 h [ 13 ]. C. viridis -derived claviridic acid C showed an IC 50 value of 7.78 μg/mL for gastric cancer cells (AGS) based on an MTT assay at 72 h [ 37 ].…”

“…Marine invertebrates are abundant resources containing diverse and unique bioactive compounds with anticancer effects [ 10 ]. Soft corals are marine invertebrates without internal skeletons and are rich in several bioactive compounds showing anticancer effects [ 11 , 12 , 13 ]. For example, several Clavularia -derived bioactive compounds showed antiproliferation effects against leukemia [ 14 ], liver [ 15 ], colon [ 16 ], prostate [ 17 ], and lung cancer cells [ 13 ].…”

“…Soft corals are marine invertebrates without internal skeletons and are rich in several bioactive compounds showing anticancer effects [ 11 , 12 , 13 ]. For example, several Clavularia -derived bioactive compounds showed antiproliferation effects against leukemia [ 14 ], liver [ 15 ], colon [ 16 ], prostate [ 17 ], and lung cancer cells [ 13 ]. However, the detailed mechanisms of action have not been investigated, and their bioactive compounds may have been extracted at a low yield.…”