Marine Sponge Hippospongia Research Articles

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.

Metachromin C, a marine-derived natural compound, shows potential in antitumor activity.

Metachromin C was first isolated from the marine sponge Hippospongia metachromia and has been reported to possess potent cytotoxicity against leukemia cells. However, its antitumor activity and possible mechanisms in pancreatic cancer remain unclear. The effects of Metachromin C on cell viability were estimated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The compound demonstrated a cytotoxic effect on four pancreatic cancer cell lines (PANC-1, BxPC-3, MiaPaCa-2, and AsPC-1). The significant S phase arrest observed with Metachromin C treatment suggests its impact on DNA replication machinery. Metachromin C might interfere with the binding of Topoisomerase I (TOPO I) to DNA, inhibit TOPO I activity, prevent DNA relaxation, cause DNA damage, and consequently activate the DNA repair pathway. Additionally, anti-migration and anti-invasion abilities of Metachromin C were confirmed using the transwell assay. It also inhibited angiogenesis in human endothelial cells by reducing cell proliferation, migration, and disrupting tube formation. Moreover, Metachromin C dose-dependently inhibited the growth of intersegmental vessels, subintestinal vessels, and the caudal vein plexus in a zebrafish embryo model, confirming its inhibitory effect on new vessel formation in vivo. Taken together, Metachromin C could not only inhibit the growth of pancreatic cancer cells but also act as an anti-angiogenic compound simultaneously.

Anti-Candidal Marine Natural Products: A Review.

Candida spp. are common opportunistic microorganisms in the human body and can cause mucosal, cutaneous, and systemic infections, mainly in individuals with weakened immune systems. Candida albicans is the most isolated and pathogenic species; however, multi-drug-resistant yeasts like Candida auris have recently been found in many different regions of the world. The increasing development of resistance to common antifungals by Candida species limits the therapeutic options. In light of this, the present review attempts to discuss the significance of marine natural products in controlling the proliferation and metabolism of C. albicans and non-albicans species. Natural compounds produced by sponges, algae, sea cucumber, bacteria, fungi, and other marine organisms have been the subject of numerous studies since the 1980s, with the discovery of several products with different chemical frameworks that can inhibit Candida spp., including antifungal drug-resistant strains. Sponges fall under the topmost category when compared to all other organisms investigated. Terpenoids, sterols, and alkaloids from this group exhibit a wide array of inhibitory activity against different Candida species. Especially, hippolide J, a pair of enantiomeric sesterterpenoids isolated from the marine sponge Hippospongia lachne, exhibited strong activity against Candida albicans, Candida parapsilosis, and Candida glabrata. In addition, a comprehensive analysis was performed to unveil the mechanisms of action and synergistic activity of marine products with conventional antifungals. In general, the results of this review show that the majority of chemicals derived from the marine environment are able to control particular functions of microorganisms belonging to the Candida genus, which can provide insights into designing new anti-candidal therapies.

Hipposponols A and B, two new 9, 11-secosterols from the marine sponge Hippospongia lachne de Laubenfels

Two new 9,11-secosterols, hipposponols A (1) and B (2), together with five known analogues, aplidiasterol B (3), (3β,5α,6β)-3,5,6-triol-cholest-7-ene (4), (3β,5α,6β,22E)-3,5,6-triol-ergosta-7,22-diene (5), and one pair of inseparable C-24 epimers of (3β,5α,6β,22E)-3,5,6-triol-stigmasta-7,22-diene (6/7), were isolated from the marine sponge Hippospongia lachne de Laubenfels. The structures of isolated compounds were extensively elucidated based on HRESIMS and NMR data. Compounds 2 − 5 showed cytotoxicity against PC9 cells with IC50 values ranging from 34.1 ± 0.9 to 38.9 ± 1.0 µM and compound 4 displayed cytotoxicity against MCF-7 cells with IC50 value of 39.0 ± 0.4 µM.

Hippobutenolides A and B, two new long-chain fatty acid esters from the marine sponge Hippospongia lachne

Two new fatty acid esters, hippobutenolides A (1) and B (2), featuring a long linear aliphatic chain attached to a butanolide residue, together with two known related ones (3 and 4), were isolated from the marine sponge Hippospongia lachne. The structures of all compounds were determined by extensive spectroscopic analysis and modified Mosher’s method. All isolates were evaluated for cytotoxicity against three non-small cell lung cancer (NSCLC) cells (A549, PC9, and HCC827) as well as one cisplatin-resistant NSCLC cell (A549-DDP) and two gefitinib-resistant NSCLC cells (PC9-GR and HCC827-GR). Compound 3 displayed cytotoxicity against all cell lines with IC50 values ranging from 18.86 to 33.24 μM.

A new meroterpene lactone and a new alkyl amino alcohol from the Vietnamese marine sponge Hippospongia fistulosa Lendenfeld, 1889

AbstractFrom the methanol extract of the marine sponge Hippospongia fistulosa Lendenfeld, 1889, a new meroterpene lactone named as hippolactone A (1), a new alkyl amino alcohol named as 2‐aminotetradec‐13‐ene‐3,4,5,6,7‐pentaol (2), and three known meroterpenes, polyfibrospongol A (3), polyfibrospongol B (4), and 19‐hydroxy‐polyfibrospongol B (5), were isolated. Their structures were elucidated by extensive spectroscopic analyses including IR, HR‐ESI‐MS, 1D and 2D NMR, and by comparison of the spectral data with those of previously reported data. Compounds 1 and 2 exhibited cytotoxic effects on Hep‐G2, MCF‐7, SK‐LU‐1, and SK‐Mel‐2 human cancer cells with percentages of dead cells in the range from 18.2±1.1 % to 43.4±1.6 %.

Hippotulosas A-D: four new sesterterpenes from marine sponge Hippospongia fistulosa Lendenfeld, 1889

Four new sesterterpenes, named as hippotulosas A-D (1–4), and a known sesterterpene furospinulosin-1 (5) were isolated from the marine sponge Hippospongia fistulosa by various chromatographic methods. Their structures were established by extensive spectroscopic analyses (IR, HR-ESI-MS, 1D and 2D NMR) and by comparison of the spectral data with those reported in the literature.

12-Deacetyl-12-epi-Scalaradial, a Scalarane Sesterterpenoid from a Marine Sponge Hippospongia sp., Induces HeLa Cells Apoptosis via MAPK/ERK Pathway and Modulates Nuclear Receptor Nur77.

12-Deacetyl-12-epi-scalaradial, a scalarane sesterterpenoid from a marine sponge Hippospongia sp, has been reported to possess cytotoxic activity on HepG2, MCF-7, and HCT-116 cells. However, there is no research to indicate that 12-deacetyl-12-epi-scalaradial exhibited anticancer effect on cervical cancer HeLa cells. The aim of this study was to investigate the anticancer activity of 12-deacetyl-12-epi-scalaradial against HeLa cells and to explore the mechanism. The results from a methylthiazolyldiphenyl-tetrazolium (MTT) assay suggested that 12-deacetyl-12-epi-scalaradial suppressed the proliferation of HeLa cells and flow cytometry analysis showed 12-deacetyl-12-epi-scalaradial could induce the apoptosis of HeLa cells in dose- and time-dependent manner. Western blotting analysis demonstrated that 12-deacetyl-12-epi-scalaradial triggered apoptosis via mediating the extrinsic pathway and was found to suppress MAPK/ERK pathway which was associate with cancer cell death. Nur77, a critical number of orphan nuclear receptors, plays diverse roles in tumor development as a transcription factor and has been considered as a promising anticancer drug target. The dual-luciferase reporter assays suggested that 12-deacetyl-12-epi-scalaradial could selectively enhance the trans-activation activity of Nur77. Furthermore, Western blotting analysis and fluorescence quenching showed that 12-deacetyl-12-epi-scalaradial could induce the phosphorylation of Nur77 and interact with the ligand-binding domain (LBD) of Nur77. Our research confirmed 12-deacetyl-12-epi-scalaradial as a potential agent for cervical cancer therapy and provided a view that 12-deacetyl-12-epi-scalaradial may be a modulator of Nur77.

(±)‐Hippolide J – A Pair of Unusual Antifungal Enantiomeric Sesterterpenoids from the Marine Sponge Hippospongia lachne

A pair of enantiomeric sesterterpenoids, (±)‐hippolide J (1a and 1b), were isolated from the marine sponge Hippospongia lachne collected from the South China Sea. The racemic mixture was resolved into a pair of enantiomers, (–)‐1a and (+)‐1b, by chiral HPLC separation. The structures of the enantiomers were determined through ESI‐HRMS and NMR spectroscopic analysis, and their absolute configurations were determined by comparison between the calculated and experimental electronic circular dichroism (ECD) spectra. Hippolide J (1) features an unusual bicyclo[4.2.0]octene core and contains three functional groups, namely, a hydroxymethyl group, an α,β‐unsaturated γ‐lactone fragment, and a characteristic prenyl side‐chain. The evaluation of the antifungal activity of (–)‐1a and (+)‐1b revealed that both show potent antifungal activity against three strains of hospital‐acquired pathogenic fungi, namely, Candida albicans SC5314, Candida glabrata 537, and Trichophyton rubrum Cmccftla, with MIC50 (minimum concentration to give 50 % inhibition) values of 0.125–0.25 µg/mL.

Unusual Anti-allergic Diterpenoids from the Marine Sponge Hippospongia lachne

Hipposponlachnins A (1) and B (2), possessing an unprecedented tetracyclo [9.3.0.02,8.03,7] tetradecane ring system, and the probable biogenetic precursor [3, (1R*,2E,4R*,7E,10S*,11S*,12R*)-10, 18-diacetoxydolabella-2,7-dien-6-one] of 1‒2 were isolated from the South China Sea marine sponge Hippospongia lachne. The structures of the novel compounds were determined using integrated spectroscopic methods in combination with single-crystal X-ray diffraction analysis. Compounds 1‒2 showed potent inhibitory activity on the release of β-hexosaminidase, a biomarker for degranulation, as well as the production of pro-inflammatory cytokine IL-4 and lipid mediator LTB4 in DNP-IgE-stimulated RBL-2H3 cells.

A Norsesterterpene Peroxide from a Marine Sponge Hippospongia sp

One new norsesterterpene peroxide, rhopaloic acid H (1), along with two known related metabolites 2 and 3, were isolated from a marine sponge Hippospongia sp. The structures of compounds were elucidated by means of IR, MS, and NMR techniques and comparison of the NMR data with those of known analogues. Evaluation of the cytotoxicities revealed that compound 2 exhibited significant cytotoxicity against DLD-1, Molt 4, T47D and K-562 cell lines, with IC50 values of 3.18, 0.69, 2.22 and 1.06 µg/mL, respectively. Moreover, compound 3 also showed significant K562 inhibitory activity, with IC50 value of 3.65 µg/mL.

New hippolide derivatives with protein tyrosine phosphatase 1B inhibitory activity from the marine sponge Hippospongia lachne.

Five new sesterterpenoids, compounds 1–5, have been isolated from the sponge Hippospongia lachne off Yongxing Island in the South China Sea. The structures of compounds 1–5 were elucidated through extensive spectroscopic analysis, including HRMS, 1D, and 2D NMR experiments. The stereochemistry, including absolute configurations of these compounds, was determined by spectroscopic, chemical, and computational methods. Compounds 1 and 5 showed moderate protein tyrosine phosphatase 1B (PTP1B) inhibitory activities with IC50 values of 5.2 μM and 8.7 μM, respectively, more potent than previously reported hippolides.

Three bioactive sesquiterpene quinones from the Fijian marine sponge of the genus Hippospongia

A sesquiterpenoid quinone, epi-ilimaquinone (1), and two sesquiterpene amino quinones, smenospongine (2) and glycinylilimaquinone (3), were isolated from the Fijian marine sponge Hippospongia sp. The structures of these compounds were determined by spectroscopic analysis. Compounds 1 and 3 were reported for the first time in this study from the sponge of the genus Hippospongia. Compound 1 displayed potent cytotoxic activity and showed antibacterial activity against methicillin-resistant Staphylococcus aureus, wild type S. aureus and vancomycin-resistant Enterococcus faecium and displayed antifungal activity against amphotericin-resistant Candida albicans while compounds 2 and 3 showed moderate cytotoxic activity. However, compound 1 did not show appreciable antifungal activity against wild type C. albicans, Cryptococcus neoformans, Aspergillus niger, Penicillium sp., Rhizopus sporangia or Sordaria sp.

Salaramides A and B; Two α-Oxoamides Isolated from the Marine Sponge Hippospongia sp. (Porifera, Dictyoceratida)

Two novel alpha-oxoamides, salaramide A (1) and its homologue salaramide B (2), were isolated from the Madagascar marine sponge, Hippospongia sp., collected in Salary Bay, north of Tulear. The structures of 1 and 2 were elucidated by interpretation of mass spectra, 1D and 2D NMR spectra, and confirmed by chemical transformation.

A sesquiterpene quinone, 5-Epi-smenospongine, promotes TNF-α production in LPS-stimulated RAW 264.7 Cells.

Eight sesquiterpene quinones: ilimaquinone (1), smenospongidine (3), smenospongiarine (5), smenospongine (7), and their corresponding 5-epimers 2, 4, 6, and 8, isolated from the Palauan marine sponge Hippospongia sp., were examined regarding their effects on TNF-α production in LPS-stimulated RAW 264.7 cells. 5-Epi-smenospongine (8) promoted the production of TNF-α to a level three times greater than the control at 10 micron, but compounds 1-7 did not show apparent activity. The results suggest that the cis-decaline ring and a primary amine in the benzoquinone ring are necessary for activity. This is the first study to report the modulation of TNF-α production by a sesquiterpene quinone.

A Sesquiterpene Quinone, 5-Epi-smenospongine, Promotes TNF-α Production in LPS-stimulated RAW 264.7 Cells

Eight sesquiterpene quinones: ilimaquinone (1), smenospongidine (3),smenospongiarine (5), smenospongine (7), and their corresponding 5-epimers 2, 4, 6, and 8,isolated from the Palauan marine sponge Hippospongia sp., were examined regarding theireffects on TNF-α production in LPS-stimulated RAW 264.7 cells. 5-Epi-smenospongine(8) promoted the production of TNF-α to a level three times greater than the control at10 μM, but compounds 1-7 did not show apparent activity. The results suggest that thecis-decaline ring and a primary amine in the benzoquinone ring are necessary for activity.This is the first study to report the modulation of TNF-α production by a sesquiterpenequinone.

Sesquiterpene Quinones from a Marine Sponge Hippospongia sp. that Inhibit Maturation of Starfish Oocytes and Induce Cell Cycle Arrest with HepG2 Cells

Bioassay-guided isolation of the marine sponge Hippospongia sp. collected at Palau led to the isolation of three sesquiterpene quinone metabolites. They were determined as ilimaquinone (1), 5-epi.-ilimaquinone (2), and 5-epi.-isospongiaquinone (3) by NMR data analysis. Compounds 2 and 3 were obtained as a mixture (ca. 4:1). The cytotoxicity on human tumor cell lines of NCI-H460, HepG2, SF-268, MCF-7, HeLa, and HL-60, inhibitory effects on starfish oocytes maturation, and cell cycle arrest on HepG2 cell line for all compounds were evaluated.

Antimicrobial Activity of Untenospongin B, a Metabolite from the Marine Sponge Hippospongia communis collected from the Atlantic Coast of Morocco

(-)-Untenospongin B isolated from the marine sponge Hippospongia communis has been tested for its antimicrobial activity against bacteria and human pathogenic fungi using agar disk method and was found to possess a broad and strong activity toward the test organisms. Its antifungal activity was further characterized by determination of the minimum inhibitory concentration (MIC) against five fungal species using broth microdilution method.

Novel sesterterpenoid and norsesterterpenoid RCE-protease inhibitors isolated from the marine sponge Hippospongia sp.

Barangcadoic acid A ( 1 ) and rhopaloic acids D ( 5 ) to G ( 8 ), novel terpenoids with RCE protease inhibitory activity, have been isolated from the marine sponge Hippospongia sp. collected in Indonesia. The structures of 1 and 5– 8 were elucidated by analysis of spectroscopic data.

New sesquiterpene hydroquinones from a Taiwanese marine sponge, Hippospongia metachromia.

In addition to metachromins A (1), B (2), and E (9), two new sesquiterpene hydroquinones, hippochromins A and B (3, 4), were isolated from the Taiwanese marine sponge Hippospongia metachromia. The structures of 4--6 were established by extensive 2D NMR analysis. Metachromins A (1) and B (2), hippochromin A diacetate (5), and metachromin B monoacetate (8) exhibited potent cytotoxicities against human colon (COLO-205) and nasopharyngeal (KB) tumor cells, while compounds 6, 7, and 9 were inactive.