Cembranoids of Soft Corals:Recent Updates and Their Biological Activities

Soft corals are well-known as excellent sources of marine-derived natural products.Among them,members of the genera Sar-cophyton,Sinularia,and Lobophytum are especially attractive targets for marine natural product research.In this review,we reported the marine-derived natural products called cembranoids isolated from soft corals,including the genera Sarcophyton,Sinularia,and Lobophytum.Here,we reviewed 72 reports published between 2016 and 2020,comprising 360 compounds,of which 260 are new compounds and 100 are previously known compounds with newly recognized activities.The novelty of the organic molecules and their relevant biological activities,delivered by the year of publication,are presented.Among the genera presented in this report,Sarcophyton spp.produce the most cembranoid diterpenes;thus,they are considered as the most important soft corals for marine natural product research.Cembranoids display diverse biological activities,includ-ing anti-cancer,anti-bacterial,and anti-inflammatory.As cembranoids have been credited with a broad range of biological activities,they present a huge potential for the development of various drugs with potential health and ecological benefits.

Marine soft corals as source of lead compounds for anti-inflammatories

Marine soft corals are known to produce a wide array of secondary metabolites,particularly diterpenoids and steroids,and often characterized by uncommon structural features and potent bioactivities.The remarkable abundance and diversity of bioactive small molecule which have been isolated from soft corals have made these organisms an important source of new drug candidates for human diseases,particularly for their anti-inflammatory activity.In this paper,the authors reported anti-inflammatory marine natural products isolated from diverse species of soft corals determined in vitro by their inhibition of lipopolysaccharide-induced expression of inducible NO synthase and cyclooxygenase-2 in murine macrophage cells(RAW 264.7).

Novel Anti-fouling Strategies of Live and Dead Soft Corals(Sarcophyton trocheliophorum):Combined Physical and Chemical Mechanisms

At present,biomimetic antifouling research objects are mostly concentrated on the fast-moving marine organism,but the anti-fouling effect of the low-speed or static marine equipment is not obvious.This paper describes the anti-fouling mechanism of soft coral(Sarcophyton trocheliophorum),including the physical defense mechanism and the bactericidal ability of mucus and coral powder.As a sessile organisms,soft coral lacks escape mechanism.Therefore,the study on its antibacterial strategy is significant because it can provide theoretical guidance for static antifouling.Results showed that the live soft coral would molt in unfriendly environment,and the secreted mucus could defend themselves against fouling microorganism.Then,Liquid Chromatography-Mass Spectrometry(LC-MS)analysis was conducted to identify the bioactive compounds of the coral powder and mucus.Results revealed that both powder and mucus contained a wide variety of toxic components,which had bactericidal effects.Moreover,at the same concentration,the inhibitory effect of the main components on Gram-negative bacteria was stronger than that on positive bacteria.These findings enhance the understanding about the antifouling mechanism of soft coral and provide new ideas for design and prepare novel antifouling strategy to combat biofouling under static condition.

A New Ceramide from the Soft Coral Cladiella humesi Verseveldt

A new ceramide, humesamide, was isolated from the soft coral Cladiella humesi Verseveldt, which was collected from Linshui County of Hainan Province. Its structure was established by spectroscopic analysis and chemical degradation methods.

Further New Highly Oxidative Cembranoids from the Hainan Soft Coral Sarcophyton trocheliophorum

Three new highly oxidative cembranoids,sarcophytrols D-F(1-3),were obtained from the South China Sea soft coral Sarcophyton trocheliophorum,along with two known related ones(4 and 5).Their structures were elucidated by extensive spectroscopic analyses and by comparison with literature data.The discovery of these new secondary metabolites enriched the family of cembranoids deduced from the title animal.

Two New Constituents from the Soft Coral Nephthea hainansis

Two new compounds, namely 7α, 10α-dimethyl-3β-isopropene-1, 2-ene-octahydro- naphthalene (1) and ethyl 5Z,8Z,11Z,14Z-nonadecatetraenoate (2) were isolated from the soft coral Nephthea hainansis. Compound 1 was a pseutosesquiterpene and 2 was a polyunsaturated fatty acid ethylate. Their structures were established on the basis of spectroscopic methods.

Nanjiols D and E, Two New Uncommon Steroids from the Chinese Soft Coral Nephthea bayeri

Two new steroids, nanjiols D and E, were isolated from the soft coral Nephthea bayeri. Their structures were characterized by spectroscopic methods and comparison with known compounds.

A NEW NOR-SESQUITERPENOID FROM THE SOFT CORAL PARALEMNaLIA THYRSOIDS

A rare nor-sesquiterpenoid with a γ-spirolactone, pathyiactone A(1), was isolated from the soft coral Paralemnalia thysoides. The structure and absolute stereochemistry of 1 was established by spectral analysis, especially 2D NMR and difference NOE studies, and CD method.

NEPHTIXAMIDE A AND B FROM THE SOFT CORAL NEPHTHEA TIXIERAE VERSEVELDT

Two new ceramides,Nephtixamide A and B,were isolated from the soft coral Nephthea tixierae verseveldt.Their structures were established by spectroscopic methods

Furanocembranoid from the Okinawan soft coral Sinularia sp.

One new furanocembranoid diterpene,11-hydroxy-Δ^(12(13))-pukalide(1),along with six known secondary metabolites,11-acetoxy-Δ^(12(13))-pukalide(2),13α-acetoxypukalide(3),pukalide(4),3α-methoxyfuranocembranoid(5),Δ9(15)-africanene(6),and methyl(5′E)-5-(2′,6′-dimethylocta-5′,7′-dienyl)furan-3-carboxylate(7)were isolated from the Okinawan soft coral Sinularia sp.Their chemical structures were elucidated based on spectroscopic analysis(FTIR,NMR,and HRESIMS),and the relative stereochemistry of 1 was determined by NOESY experiments and acetylation,which yielded derivative 2.In addition,compounds 1 and 7 exhibited toxicity in the brine shrimp lethality test.

Sarcocinerenoids A—J,Eight Rare Capnosane-Type and Two New Cage-Type Cembranoids with Promoting Angiogenesis Activity from the South China Sea Soft Coral Sarcophyton cinereum

Backgroundand Originality Content,Cembranoids are a structurally diverse class of diterpenoids commonly occurring in marine and terrestrial organisms.(+)-Cembrene was the first reported cembranoid diterpenoid discovered in 1962,l and more than 1400 cembranoid diterpenoids have been identified in the last six decades,[2]Cembranoids are characterized by a 14-membered carbocyclic ring,an isopropyl group and three methyl groups,which form their core carbon skeleton.Enzymatic processes such as oxidation,oxidative rearrangements and transannular cyclizations occur in organisms,leading to the formation of distinctive specialized metabolites such as epoxide,lactone,ester,furan,pyrane and other ringbased cembranoids.[2-3]

The Identification of Two New Sterols from Marine Organism

Two new sterol have been isolated from the South China Sea marine organism. Compound 1 was isolated from the sponge Polymastia sobustia and compound 2 was obtained from the soft coral Sinularia inexplicata. Their structures were established as 3 beta-hydroxy-stigmast-5en-7-one and 24-methylene cholestan -3 beta, 6 beta, 9 alpha, 19-tetrol by variety of spectral analysis such as IR, EIMS, 1DNMR, H-1-H-1 COSY, HMQC, HMBC, NOESY.

Clavukoelloids A—M,Thirteen Rare N-Containing Nardosinane Type Sesquiterpenoids from the Soft Coral Clavularia koellikeri

Thirteen new nitrogen-containing nardosinane-type sesquiterpenoids,clavukoelloids A-M(1-13)with unique acrylamide fragments vs.the reported general nardosinane-type sesquiterpenoids containing lactone,were isolated from the soft coral Clavularia koellikeri collected from the South China Sea.The structures and absolute configurations of new compounds were unambiguously determined by analysis of spectroscopic data,CP3,DP4+,ECD spectra,and X-ray diffraction.Compound 6 showed anti-inflammatory activities and hepatoprotective activities in transgenic fluorescent zebrafish.

Four new steroids from the marine soft coral-derived fungus Penicillium sp. SCSIO41201

Penicildiones A-D(1-4), four new steroids derivatives together with three known compounds including 16α-methylpregna-17α,19-dihydroxy-(9,11)-epoxy-4-ene-3,18-dione-20-acetoxy(5), stachybotrylactone B(6) and stachybotrin(7) were isolated from the soft coral-derived fungus Penicillium sp. SCSIO41201, cultured in the 1% NaCl PDB substrate. Their structures were determined through spectroscopic methods and X-ray crystallography. Biological evaluation results revealed that 6 exhibited significant cytotoxic activity against HL-60, K562, MOLT-4, ACHN, 786-O, and OS-RC-2 cell lines with IC50 values of 5.23, 4.12, 4.31, 23.55, 7.65 and 10.81 μmol·L-1, respectively, while other compounds showed weak or no cytotoxicity at 50 μmol·L-1.

Uncommon Polycyclic Merosesquiterpenoids and Asteriscanoids from the Hainan Soft Coral Sinularia hurnesi

A rare highly fused racemic merosesquiterpenoid,9-epi-verrubenzospirolactone(1),six new asteriscane-type sesquiterpenoids,sinuhumesins A-F(4-9),and two related known ones(10 and 11)were isolated from Hainan soft coral Sinularia humesi.Compound 1 was further separated by chiral HPLC resolution to one pair of enantiomers[(+)-1 and(-)-1],respectively.The full structures of the new compounds were unambiguously determined by extensive spectroscopic analysis,chemical computation approaches,modified Mosher's method and/or X-ray diffract!on analysis,as well as comparison with previously reported data of related model compounds.

Cembranoid, Steroid, and Sesquiterpenoid Derivatives from the South China Sea Soft Coral Sinularia numerosa

Two new cembranoids, namely, sinumerolides A and B （1 and 2）, one new steroid, 7fl-hydroxygorgosterol （7）, along with four known cembranoid derivatives （3-6）, four known steroids （8-11）, and four known africane ses- quiterpenoids （12-15）, were isolated and identified from the marine soil coral Sinularia numerosa that was col- lected from South China Sea waters. The structures of these metabolites were elucidated on the basis of extensive spectroscopic analysis and by comparison of their spectral data with those of literature reports. The isolated com- pounds were evaluated for the antimicrobial and cytotoxic activity.

Polyoxygenated Cembranoids from Soft Coral Lobophytum Crassum and Their Anti-tumoral Activities

Main observation and conclusion Four new cembranoids,6-oxo-cembrene-A(1),lobocrassins G-H(2-3),and 14-epi-lobophytolide B(4),along with eight known re-lated compounds(5-12),were isolated from the South China Sea soft coral Lobophytum crassum.Their structures were established by extensive spectroscopic analysis and by comparison of the spectral data with those reported in the literatures.The absolute stere-ochemistry of 14-epi-lobophytolide B(4)was established by time-dependent density functional theory electronic circular dichroism(TDDFT-ECD)calculations,whereas that of three known metabolites(6,11 and 12)was also determined,for the first time,by using modified Mosher's method and/or X-ray diffraction analyses.In bioassay,the cembranoids 6,7 and 12 showed significant an-ti-tumoral activity against A549,HT-29,SNU-398 and Capan-1 tumor cell lines with IC_(50) values ranging from 1.5 to 7.4μmol/L.A pre-liminary structure-activity relationship was also discussed.

Polyoxygenated anti-inflammatory biscembranoids from the soft coral Sarcophyton tortuosum and their stereochemistry

Five novel biscembranoids,ximaolides H-L(1-5),along with four known related compounds(6-9) were isolated from the Hainan soft coral Sarcophyton tortuosum.The structures of the new compounds were determined by extensive spectroscopic analysis,quantum chemical calculations,and/or by comparing their CD spectra with those of the known compounds.Compounds 1 and 2 are the first examples of biscembranoids bearing a 1,35-bridged lactone moiety,4 is the first biscembranoid comprising an uncommon oxetane ring,and 5 represents the first 36-peroxyl biscembranoid.Ximaolides Ⅰ(2),K(4) and F(9) exhibited interesting anti-inflammatory activity by the inhibition of LPS-induced TNF-α protein release in RAW264.7 macrophages.

New lobane-type diterpenoids from the Xisha soft coral Sinularia polydactyla

Lobane-type diterpenoids are not frequently discovered from marine soft corals. In this paper, three new lobane type diterpenes, 13-methoxyloba-8,10,15(16),17(18)-tetraene(1), 8,10,13(15)Z,16 E-lobatetraene(2) and 19-hydroxy-lobatetraene(3), and a new natural compound, 17,18-epoxyloba-16-acetoxy-8,10,13(15)-trien(4), co-occurring with a known related diterpenoid, 18-methoxyloba-8,10,13(15),16(17)-tetraene(5), were isolated from the South China Sea soft coral Sinularia polydactyla. The structures of new compounds were determined by extensive spectroscopic analysis and by comparison with those reported in the literature. In bioassay, all the isolates were inactive on antibacterial, PTP1 B inhibitory, and immunological activities. This study increased the chemical diversity of marine diterpenoids.

A Novel Diterpenoid from the Soft Coral Sarcophyton crassocaule

A novel hydroperoxide cembrane-type diterpenoid was isolated from the soft coral Sarcophyton crassocaule collected from the Xisha Islands in the South China Sea. The structure of 3 was established by spectroscopy and X-ray diffraction analysis,named as sarcophyocrassolide A. It exhibited strong cytotoxicity against the P-388 cell line with IC_ 50 value of 0.1 μg/mL.