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

Abstract

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 Mosher's 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.

Flexibilide Obtained from Cultured Soft Coral Has Anti-Neuroinflammatory and Analgesic Effects through the Upregulation of Spinal Transforming Growth Factor-β1 in Neuropathic Rats

“…The method of flexibilide extraction was modified from that of Lu et al [94,95]. The specimens were extracted with 95% ethanol.…”

Cembranoid-Related Metabolites and Biological Activities from the Soft Coral Sinularia flexibilis

“…In previous studies of the chemical constituents of Taiwanese soft corals, numerous marine metabolites with cytotoxic [14,15], neuroprotective [16], and anti-inflammatory activities [17,18,19] were also found from Sinularia flexibilis . Some cembranolides, possessing an α-methylene lactone ring, have been discovered as potent cytotoxic agents to a limited panel of cancer cell lines, for example, 14-deoxycrassin [20], and as significant anti-inflammatory agents, for example, sinulariolone acetate [21]. Additionally, cembranoids and related compounds from other coral species were also found to have notable antiviral [22], anti-inflammatory [23,24], and antiproliferative [25,26,27,28] activities.…”

“…flexibilis , collected off the waters of Taiwan. Herein, we report the isolation of five new cembrane-related metabolites, namely, flexbilisins D and E ( 1 and 2 ), secoflexibilisolides A and B ( 3 and 4 ), and a cembranolide flexibilisolide H ( 5 ) (Figure 1), and nine known compounds, including 6 R -hydroxysinulariolide ( 6 ) [3], 11-dehydrosinulariolide ( 7 ) [18], 11- epi -sinulariolide acetate ( 8 ) [13], 14-deoxycrassin ( 9 ) [20], 3,4:8,11-bisepoxy-7-acetoxycembra-15(17)-en-1,12-olide ( 10 ) [6], sinulariolide ( 11 ) [2], sinulaflexiolide E ( 12 ) [10], querciformolide A ( 13 ) [21], and flexibilisquinone ( 14 ) [19] (Figure 2). Their structures were established by spectroscopic analysis including infrared (IR), mass spectrometry (MS), and nuclear magnetic resonance (NMR) data (Figures S1–S14), as well as chemical transformation.…”

Bioactive Cembrane Derivatives from the Indian Ocean Soft Coral, Sinularia kavarattiensis

“…The coral species of the genus, Sinularia , are widespread in coral reefs all over the world and have been reported to contain a variety of compounds with novel chemical structures [14]: sesquiterpenes [15,16], diterpenes [17], in particular cembranoids and norcembranoids, and polyhydroxylated steroids [18], which possess unique structural diversity. These metabolites display potential bioactivities, such as antimicrobial [14], anti-inflammatory [19,20,21,22,23,24], antiviral [25] and cytotoxic activity [26,27,28]. In the present study, the enriched chloroform extract of S. kavarattiensis afforded four known 14-membered macrocyclic norcembranoids, 1 – 4 (5- epi -sinuleptolide [29], sinuleptolide [30], scabrolide D [31,32] and norcembranoid 4 [33]), all of which lack a C-18 carbon substituent in their structures; one known germacrane-type sesquiterpenoid, 5 ( ent -germacra-4(15),5 E ,10(14)-trien-1β-ol) [34], one known C 19 -norcembranoid diterpene ineleganolide, 6 [35], and the novel norcembranoid, named kavaranolide 7 (Figure 1), possessing a tricyclic carbocycle with the trans -fused six and seven-membered rings.…”

“…Corals of the genus, Sinularia , are, however, well-known sources of anti-inflammatory agents [19,20,21,22,23,24]. The isolated compounds were therefore, in addition to anti-CHIKV replicon activity, also studied for potential anti-inflammatory activity in primary microglial cells that serve as a model for neuroinflammation.…”