Isolation and absolute configuration of alkylpyridine alkaloids from the marine sponge Hippospongia lachne.

Marine sponges are well known as prolific producers of structurally diverse molecules with valuable pharmacological potential. As part of our ongoing program to discover bioactive compounds from marine sponges collected from the Xisha Islands in the South China Sea, a chemical study on the specimens of Hippospongia lachne was conducted. As a result, eight undescribed compounds, including four zwitterionic alkylpyridinium salts, hippospondines A-D (1-4), and four 3-alkylpyridine alkaloids, hippospondines E (5), F (6), and (±)-hippospondine G (7), were isolated from the marine sponge H. lachne, together with one known 3-alkylpyridine alkaloid (8). The undescribed structures were elucidated by HRESIMS, NMR, DP4+ and CP3 probability analysis, and the Snatzke's method. Hippospondines A-D (1-4) represent the rare example of inner salt type alkylpyridinium alkaloid with a farnesyl moiety. Compounds 1-3 and 8 were subjected to cytotoxic and lymphocyte proliferation assays. Compound 3 exhibited a weak promotion effect on the ConA-induced T lymphocyte proliferation.

Arenarialins A-F, Anti-inflammatory Meroterpenoids with Rearranged Skeletons from the Marine Sponge Dysidea arenaria.

Six new sesquiterpene quinone/hydroquinone meroterpenoids, arenarialins A-F (1-6), were isolated from the marine sponge Dysidea arenaria collected from the South China Sea. Their chemical structures and absolute configurations were determined by HRMS and NMR data analyses coupled with DP4+ and ECD calculations. Arenarialin A (1) features an unprecedented tetracyclic 6/6/5/6 carbon skeleton, whereas arenarialins B-D (2-4) possess two rare secomeroterpene scaffolds. Arenarialins A-F showed inhibitory activity on the production of inflammatory cytokines TNF-α and IL-6 in LPS-induced RAW264.7 macrophages with arenarialin D regulating the NF-κB/MAPK signaling pathway.

Dysambiol, an Anti-inflammatory Secomeroterpenoid from a Dysidea sp. Marine Sponge.

An unusual secomeroterpenoid, dysambiol (1), was isolated from a Dysidea sp. marine sponge collected from the South China Sea. Dysambiol features an unprecedented secomeroterpene scaffold with a rare lactone bridge. The structure of 1 was determined by extensive spectroscopic analysis, Mosher's method, and electronic circular dichroism calculation. Dysambiol displayed potent anti-inflammatory activity in LPS-induced Raw 264.7 macrophages by regulating the NF-κB/MPAK signaling pathway.

Aspergetherins A-D, New Chlorinated Biphenyls with anti-MRSA Activity from the Marine Sponge Symbiotic Fungus Aspergillus terreus 164018.

Aspergetherins A-D (1-4), four new chlorinated biphenyls, were isolated from the rice fermentation of a marine sponge symbiotic fungus Aspergillus terreus 164018, along with seven known biphenyl derivatives (5-11). The structures of four new compounds were determined by a comprehensive analysis of the spectroscopic data, including HR-ESI-MS and 2D NMR data. All 11 isolates were evaluated for their anti-bacterial activity against two strains of methicillin-resistant Staphylococcus aureus (MRSA). Among them, compounds 1, 3, 8 and 10 showed anti-MRSA activity with MIC values of 1.0-128 µg/mL. Preliminary structure-activity relationship analysis unveiled that both chlorinated substitution and esterification of 2-carboxylic acid could impact the antibacterial activity of biphenyls.

New Spiro-Sesquiterpenoids from the Marine Sponge Myrmekioderma sp.

Three new spiro-sesquiterpenoids, myrmekiones A-C (1-3), were isolated from the marine sponge Myrmekioderma sp. collected from the South China Sea. The structures of 1-3 were experimentally illuminated though comprehensive NMR spectra, X-ray diffraction analysis and calculated ECD. These three compounds possessed a special spiro skeleton. Compound 1 was characterized by a chamigrane-type structure, it is the first time to obtain the single-crystal of this type of oil compounds. 2 and 3 were a pair of diastereoisomers that possessed an acorane skeleton. This study expands the chemical diversity of marine origin spiro-metabolites.

Terpenoids from the South China Sea soft coral Sinularia multiflora.

A rare sinulariane-type norcembranoid sinulariadiolide B (1) with a unique cyano group, and a eunicellin-based diterpenoid multifloralin (2), along with two known related analogues, sinulariadiolide (3) and sclerophytin E (4), were isolated from the extract of the South China Sea soft coral Sinularia multiflora. Their structures were elucidated on the basis of detailed spectroscopic analysis and by comparison with previously reported data. Compounds 2 and 4 showed potent antifouling activity against barnacle Balanus albicostatus.

Combinational protective therapy for spinal cord injury medicated by sialic acid-driven and polyethylene glycol based micelles.

Spinal cord injury (SCI) leads to immediate disruption of neuronal membranes and loss of neurons, followed by extensive secondary injury process. Treatment of SCI still remains a tremendous challenge clinically. Minocycline could target comprehensive secondary injury via anti-inflammatory, anti-oxidant and anti-apoptotic mechanisms. Polyethylene glycol (PEG), a known sealing agent, is able to seal the damaged cell membranes and reduce calcium influx, thereby exerting neuroprotective capacity. Here, an E-selectin-targeting sialic acid - polyethylene glycol - poly (lactic-co-glycolic acid) (SAPP) copolymer was designed for delivering hydrophobic minocycline to achieve combinational therapy of SCI. The obtained SAPP copolymer could self-assemble into micelles with critical micelle concentration being of 13.40 µg/mL, and effectively encapsulate hydrophobic minocycline. The prepared drug-loaded micelles (SAPPM) displayed sustained drug release over 72 h, which could stop microglia activation and exhibited excellent neuroprotective capacity in vitro. The SAPP micelles were efficiently accumulated in the lesion site of SCI rats via the specific binding between sialic acid and E-selectin. Due to the targeting distribution and combinational effect between PEG and minocycline, SAPPM could obviously reduce the area of lesion cavity, and realize more survival of axons and myelin sheaths from the injury, thus distinctly improving hindlimb functional recovery of SCI rats and conferring superior therapeutic effect in coparison with other groups. Our work presented an effective and safe strategy for SCI targeting therapy. Besides, neuroprotective capacity of PEG deserves further investigation on other central nervous system diseases.

Aplysinopsin-type and Bromotyrosine-derived Alkaloids from the South China Sea Sponge Fascaplysinopsis reticulata.

Seven pairs of new oxygenated aplysinopsin-type enantiomers, (+)- and (-)-oxoaplysinopsins A‒G (1‒7), two new bromotyrosine-derived alkaloids, subereamollines C and D (18 and 19), together with ten known compounds (8‒17) were isolated from the Xisha Islands sponge Fascaplysinopsis reticulata. The planar structures were determined by extensive NMR and MS spectroscopic data. Each of the optically pure enantiomers was achieved by chiral HPLC separation. The absolute configurations were assigned by the quantum chemical calculation methods. Compound 19 showed cytotoxicity against Jurkat cell lines with IC50 value of 0.88 µM. Compounds 2, 16 and 17 showed tyrosine phosphatase 1B (PTP1B) inhibition activity with IC50 value ranging from 7.67 to 26.5 µM, stronger than the positive control of acarbose and 1-deoxynojirimycin. A structural activity relationship for the aplysinopsin-type enantiomers were observed in PTP1B inhibition activity of 2 and cytotoxicity of 3 that the dextrorotary (+)-2 and (+)-3 showed stronger activity than the levorotary (-)-2 and (-)-3.

Metabolites from the Paracel Islands Soft Coral Sinularia cf. molesta.

Five new oxygenated sesquiterpenes, molestins A⁻D (1, 3⁻5) and epi-gibberodione (2), three new cyclopentenone derivatives, ent-sinulolides C, D, and F ((+)-9⁻(+)-11), one new butenolide derivative, ent-sinulolide H ((+)-13), and one new cembranolide, molestin E (14), together with 14 known related metabolites (6⁻8, (⁻)-9⁻(⁻)-11, (±)-12, (⁻)-13, 15⁻19) were isolated from the Paracel Islands soft coral Sinularia cf. molesta. The structures and absolute configurations were elucidated based on comprehensive spectroscopic analyses, quantum chemical calculations, and comparison with the literature data. Compound 5 is the first example of a norsesquiterpene with a de-isopropyl guaiane skeleton isolated from the genus Sinularia. Molestin E (14) exhibited cytotoxicities against HeLa and HCT-116 cell lines with IC50 values of 5.26 and 8.37 µM, respectively. Compounds 4, 5, and 8 showed significant inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 218, 344, and 1.24 µM, respectively.

Terpenoids from the Soft Coral Sinularia sp. Collected in Yongxing Island.

Three new sesquiterpenoids (sinuketal (1), sinulins A and B (2 and 3)) and two new cembranoids (sinulins C and D (4 and 5)), as well as eight known sesquiterpenoids (6–13) and eight known cembranoids (14–21), were isolated from the Xisha soft coral Sinularia sp. Their structures were elucidated by extensive spectroscopic analysis. Compound 1 possesses an unprecedented isopropyl-branched bicyclo [6.3.0] undecane carbon skeleton with unique endoperoxide moiety, and a plausible biosynthetic pathway of it was postulated. According to the reported biological properties of endoperoxide, the antimalarial, cytotoxic, antiviral, and target inhibitory activities of 1 were tested. Compound 1 showed mild in vitro antimalarial activity against Plasmodium falciparum 3D7, weak cytotoxic activities toward Jurkat, MDA-MB-231, and U2OS cell lines, inhibitory effects against influenza A viruses H1N1 and PR8, as well as mild target inhibitory activity against acetylcholinesterase. The other compounds were evaluated for cytotoxicities against HeLa, HCT-116, and A549 tumor cell lines and target inhibitory activities against protein tyrosine phosphatase 1B (PTP1B). Compound 20 exhibited cytotoxicities against HeLa and HCT-116, and compounds 5, 11, and 15 showed mild target inhibitory activities against PTP1B.