Jyh-Horng Sheu

Survey of Briarane-Type Diterpenoids of Marine Origin

The structures, names, biological activities, and references of two hundred ninety-nine marine original briarane-type metabolites are described and compiled in tabular form in this review. All briarane-type natural products are obtained from marine invertebrates, including various octocorals, a nudibranch, and a sponge. Some of these compounds showed potential biological activities.

Anti-inflammatory Cembranoids from the Soft Corals Sinularia querciformis and Sinularia granosa

Four new cembranoids, querciformolides A-D (1-4), along with two known cembranoids, 7 and 8, have been isolated from the soft coral Sinularia querciformis. Furthermore, chemical investigation of Sinularia granosa has afforded three new cembranoids, querciformolide B (2) and granosolides A (5) and B (6). The structures of the new metabolites were elucidated on the basis of extensive spectroscopic methods, and that of 2 was further confirmed by X-ray diffraction analysis. The absolute configurations of 1 and 2 were determined by a modified Moshers method. Among these metabolites, 2-6 are rarely found cembranoids possessing a tetrahydrofuran moiety with a 4,7-ether linkage; in addition, 1 is the first epsilon-lactone cembrane found that possesses a tetrahydropyran moiety with a 4,8-ether linkage. None of these compounds were found to be cytotoxic toward a limited panel of cancer cell lines. However, compounds 3, 7, and 8 significantly inhibited the accumulation of the pro-inflammatory iNOS and COX-2 proteins in LPS-stimulated RAW264.7 macrophage cells.

Cytotoxic and Anti-inflammatory Cembranoids from the Soft Coral Lobophytum crassum

Five new cembranoids, namely, crassumolides A and B and D-F (1 and 2 and 4-6), along with four known metabolites, 7-10, were isolated from the soft coral Lobophytum crassum. Crassumolide C (3) was isolated for the first time from a natural source. The structures of these compounds were elucidated by extensive spectroscopic analysis and comparison of the NMR data with those of known analogues. The absolute stereochemistry of 1 was determined using the modified Moshers method. Chemical transformation of 7 into the corresponding methyl ester 3 revealed the absolute stereochemistry of 3. Compounds 1, 3, and 7 were cytotoxic toward Ca9-22 cancer cells, and 10 was broadly cytotoxic toward all six test cancer cell lines used. Compounds 1, 3, 7, and 10 were found to inhibit the accumulation of the pro-inflammatory proteins iNOS and COX-2 at 10 μM.

Five novel norcembranoids from Sinularia leptoclados and S. parva

Abstract Three new norcembrane-based diterpenoids, leptocladolides A ( 1 ), B ( 4 ) and C ( 5 ), along with five known metabolites 6 – 10 , have been isolated from the dichloromethane extract of a Taiwanese soft coral Sinularia leptoclados . Furthermore, a chemical investigation on the dichloromethane extract of S. parva has resulted in the isolation of two new related isomers, 1- epi -leptocladolide A ( 2 ) and 7 E -leptocladolide A ( 3 ), in addition to 1 and 7 . The structures of new metabolites 1 – 5 were elucidated on the basis of extensive spectroscopic analyses and their relative stereochemistries were determined by NOESY experiments. The new metabolites 1 and 3 have been shown to exhibit significant cytotoxic activity against KB and Hepa59T/VGH cancer cell lines.

A neuroprotective sulfone of marine origin and the in vivo anti-inflammatory activity of an analogue

Our continuing effort of searching bioactive substances from the Formosan soft coral Cladiella australis has led to the isolation of a bioactive substance austrasulfone (1), which possesses significant neuroprotective activities. A straightforward synthesis of 1 was achieved by a two-step reaction sequence. Dihydroaustrasulfone alcohol (3), the synthetic precursor of 1, not only exhibited in vitro anti-inflammatory activity, but also showed potent therapeutic ability in the treatment of neuropathic pain, atherosclerosis, and multiple sclerosis in rats.

Simplexins A-I, eunicellin-based diterpenoids from the soft coral Klyxum simplex.

Nine new eunicellin-based diterpenoids, simplexins A-I (1-9), were isolated from a Dongsha Atoll soft coral, Klyxum simplex. The structures of these compounds were established by detailed spectroscopic analysis (IR, MS, 1D and 2D NMR) and by comparison with the physical and spectral data of related known compounds. The absolute configuration of 1 was determined by a modified Moshers method. Compounds 1, 4, and 5 were found to be cytotoxic toward a limited panel of cancer cell lines. Compound 5 was shown to significantly inhibit the accumulation of the pro-inflammatory iNOS and COX-2 proteins in LPS-stimulated RAW264.7 macrophage cells.

Briaexcavatolides K−N, New Briarane Diterpenes from the Gorgonian Briareum excavatum

Four new briarane diterpenes, briaexcavatolides K-N (1-4), along with a known diterpene, 5, have been isolated from the Taiwanese gorgonian Briareum excavatum. The structures of the new metabolites were established by extensive spectral analyses. Furthermore, the structure, including the relative configuration of briaexcavatolide K (1), was confirmed by a single-crystal X-ray analysis. Briaexcavatolides K and L (1 and 2) are the only briarane diterpenes known to possess hydroxyl groups at the C-8beta and C-17alpha positions, respectively. Cytotoxicity of these metabolites toward various cancer cell lines also is described.

Anti-Inflammatory Activities of Natural Products Isolated from Soft Corals of Taiwan between 2008 and 2012

This review reports details on the natural products isolated from Taiwan soft corals during the period 2008–2012 focusing on their in vitro and/or in vivo anti-inflammatory activities. Chemical structures, names, and literature references are also reported. This review provides useful and specific information on potent anti-inflammatory marine metabolites for future development of immune-modulatory therapeutics.

Survey of briarane-type diterpenoids - Part IV

The structures, names, biological activities, and references of 137 briarane-type diterpenoids are summarized. All briaranes mentioned in this review article were obtained from various octocorals including the specimens belonging to the genus Briareum, Ellisella, Gorgonella, Junceella, Subergorgia, Renilla, and Pachyclavularia.

Sinularin from Indigenous Soft Coral Attenuates Nociceptive Responses and Spinal Neuroinflammation in Carrageenan-Induced Inflammatory Rat Model

Three decades ago, the marine-derived compound sinularin was shown to have anti-edematous effects on paw edema induced by carrageenan or adjuvant. To the best of our knowledge, no new studies were conducted to explore the bioactivity of sinularin until we reported the analgesic properties of sinularin based on in vivo experiments. In the present study, we found that sinularin significantly inhibits the upregulation of proinflammatory proteins, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) and upregulates the production of transforming growth factor-β (TGF-β) in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells according to western blot analysis. We found that subcutaneous (s.c.) administration of sinularin (80 mg/kg) 1 h before carrageenan injection significantly inhibited carrageenan-induced nociceptive behaviors, including thermal hyperalgesia, mechanical allodynia, cold allodynia, and hindpaw weight-bearing deficits. Further, s.c. sinularin (80 mg/kg) significantly inhibited carrageenan-induced microglial and astrocyte activation as well as upregulation of iNOS in the dorsal horn of the lumbar spinal cord. Moreover, s.c. sinularin (80 mg/kg) inhibited carrageenan-induced tissue inflammatory responses, redness and edema of the paw, and leukocyte infiltration. The results of immunohistochemical studies indicate that s.c. sinularin (80 mg/kg) could upregulate production of TGF-β1 in carrageenan-induced inflamed paw tissue. The present results demonstrate that systemic sinularin exerts analgesic effects at the behavioral and spinal levels, which are associated with both inhibition of leukocyte infiltration and upregulation of TGF-β1.