Dysifragilones A–C, Unusual Sesquiterpene Aminoquinones and Inhibitors of NO Production from the South China Sea Sponge Dysidea fragilis

Abstract

Dysifragilones A-C (1-3), three unusual sesquiterpene aminoquinones based on a rearranged avarone skeleton, were isolated from the South China Sea sponge Dysidea fragilis. Their structures were elucidated by detailed spectroscopic and spectrometric analysis, and their absolute configurations were assigned from calculated electronic circular di- [a] Key

Dysifragilone A inhibits LPS‑induced RAW264.7 macrophage activation by blocking the p38 MAPK signaling pathway

“…Samples of Dysidea fragilis were collected along the coast of Yongxing Island in the South China Sea on 11th April 2011, and the extraction, isolation and identification of dysifragilone A (15.9 mg; Fig. 1A) were performed by Shanghai Jiao Tong University (Shanghai, China) (14). Subsequently, the purity was determined by standardization of the peak area by high performance liquid chromatography, which was found to be 98.7% (via a UV detector).…”

“…The diversity of the chemical structures implies the potential of various bioactivities, such as antibacterial, anti-inflammatory, antiviral and anti-cardiovascular activity. Previous studies on marine sponges of Dysidea genus from the Xisha Islands Dysifragilone A inhibits LPS-induced RAW264.7 macrophage activation by blocking the p38 MAPK signaling pathway in the South China Sea identified seven novel sesquiterpene quinones (dysidavarones A-D and dysideanones A-C) (11,12) from Dysidea avara, and 13 novel sesquiterpene aminoquinones (dysidaminones A-M) (13) and three other novel sesquiterpene aminoquinones based on a rearranged avarone skeleton (dysifragilones A-C) (14) from Dysidea fragilis. These newly isolated agents have been assessed for their inhibitory activities on lipopolysaccharide (LPS)-stimulated production of nitric oxide (NO) in RAW264.7 cells, and the results have demonstrated that dysifragilone A exhibits potent inhibitory activity.…”

Marine Pharmacology in 2014–2015: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, Antiviral, and Anthelmintic Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…[185][186][187]; two new briarane diterpenoids briaviolides E and I (170,171), isolated from the Taiwanese soft coral Briareum violacea [188]; a new pigmented phenazine compound dermacozine H (172), isolated from the actinomycete Dermacoccus abyssi sp. nov. strain MT1.1, isolated from a Mariana Trench sediment at a depth of 10,898 m [189]; a novel sesquiterpene dysifragilone A (173), isolated from the South China Sea sponge Dysidea fragilis [190]; a new xenicane 4α-hydroxypachylactone (174), isolated from a Chinese brown alga Dictyota plectens [191]; a polyketide comaparvin (175), isolated from the Taiwanese marine crinoid Comanthus bennetti [192]; two novel eunicellin-type diterpenoids hirsutalins N and S (176, 177) and a new tocopherol-derived metabolite hirsutocospiro A (178), isolated from the Taiwanese soft coral Cladiella hirsuta [193][194][195]; a new cembranoid isosinulaflexiolide K (179), isolated from cultured Taiwanese soft corals Sinularia sandensis and Sinularia flexibilis [196]; a novel 9,11-secogorgosteroid klyflaccisteroid F (180), isolated from the Taiwaneses soft coral Klyxum flaccidum [197]; new eunicellin-type diterpenoids krempfielins N (181), Q (182), and R (183), isolated from a Taiwanese soft coral Cladiella krempfi [198,199]; a methylfarnesylquinone (184), isolated from the Taiwanese marine brown alga Homeostrichus formosana [200]; a novel steroid monanchosterol B (185), isolated from the Korean sponge Monanchora sp. [201]; a oxygenated steroid derivative (186), isolated from the Vietnamese starfish Protoreaster nodosus [202]; a new spirobisnaphthalene rhytidenone C (187), isolated from an extract of a cultured fungal endophyte Rhytidhysteron sp.…”

“…[201]; a oxygenated steroid derivative (186), isolated from the Vietnamese starfish Protoreaster nodosus [202]; a new spirobisnaphthalene rhytidenone C (187), isolated from an extract of a cultured fungal endophyte Rhytidhysteron sp. AS21B isolated from a Thailandese mangrove area [203]; a known terpenoid sarcocrassocolide E (188), isolated from a Taiwanese soft coral Sarcophyton crassocaule [204]; a new cembrane diterpenoid sinulacembranolide A (189), isolated from the Taiwanese soft coral Sinularia gaweli [205]; a new eudesmane-type sesquiterpene thomimarine B (190), isolated from the fungus Penicillium thomii KMM 4667 isolated from the Japanese sea grass Zostera marina [206]; and a novel diterpenoid tortuosene A (191), isolated from the Taiwanese soft coral Sarcophyton tortuosum [207].…”

Bioactive Prenyl- and Terpenyl-Quinones/Hydroquinones of Marine Origin †

“…Dysifragilones A-C ( 255 – 257 ) ( Figure 23 ) are other examples of the same 6-6-5-6-benzofluorene core isolated from Dysidea fragilis collected at the same place, Yongxing Island, and bearing amino substituents on the quinone fragment. They displayed potential anti-inflammatory activity through the inhibition of NO production in mouse macrophages, with dysifragilone A being the most potent compound [ 111 ].…”