Cytotoxic p-terphenyls from the deep-sea-derived Aspergillus candidus.

From the deep-sea-derived fungus Aspergillus candidus, one novel (1) and three known (2-4) p-terphenyl derivates were isolated. The structure of the new compound was established mainly on the basis of extensive analysis of 1D and 2D NMR data. All four isolates were tested for in vitro anti-food allergic and antitumor bioactivities. Compounds 3 and 4 showed potent antiproliferative effect against four cancer cells of Hela, Eca-109, Bel-7402, and PANC-1 with IC50 values ranging from 5.5 µM to 9.4 µM.

Asperochratides A-J, Ten new polyketides from the deep-sea-derived Aspergillus ochraceus.

Ten new C9 polyketides (asperochratides A-J, 1-10) and 14 known miscellaneous compounds (11-24) were isolated from the deep-sea-derived fungus Aspergillus ochraceus. Structures of the new compounds were elucidated by extensive spectroscopic analyses, modified Mosher's method, Mo2(OAc)4 induced circular dichroism (ICD) experiments, and ECD calculations. Structurally, compounds 1-11 and 16-18 share the same polyketide origin of the skeleton and belong to aspyrone co-metabolites. All isolates were tested for cytotoxic, anti-food allergic, anti-H1N1 virus, anti-microbe, and anti-inflammatory activities in vitro. Results showed that compounds 5-8 and 13-17 exerted significant cytotoxic effects on BV-2 cell line, and compound 16 showed the potential of anti-inflammatory activities.

Chemical Constituents and Bioactivities of Starfishes: An Update.

Starfishes produce various structurally unique secondary metabolites with diverse biological activities. This review is an update summary of the new compounds and their bioactivities from starfish (the Asteroidea Class) with 71 references covering from January 2007 to December 2018. During this period, 216 new compounds were obtained from 36 species. The chemical constituents are mostly steroids, steroidal glycosides, and gangliosides. These components have been found to possess various bioactivities, including anticancer, anti-inflammation, etc.

Botryotins A-H, Tetracyclic Diterpenoids Representing Three Carbon Skeletons from a Deep-Sea-Derived Botryotinia fuckeliana.

Eight unprecedent diterpenoids, botryotins A-H (1-8), were obtained from Botryotinia fuckeliana. They represent three novel carbon skeletons with 6/6/5/5 (1), 6/6/5/6 (2-6), and 6/6/6/5 (7 and 8) tetracyclic scaffolds. Their structures were determined by detailed spectroscopic analysis and chemical derivatization as well as quantum chemical calculation of the ECD and OR data. Botryotin A (1) exhibited a moderate antiallergic effect (IC50 = 0.2 mM). A plausible biosynthetic pathway for 1-8 was proposed.

Andrastone A From the Deep-Sea-Derived Fungus Penicillium allii-sativi Acts as an Inducer of Caspase and RXRα-Dependent Apoptosis.

Two new (1, 2) and one known (3) meroterpenoids were isolated from the deep-sea-derived fungus Penicillium allii-sativi. The relative structures of new compounds were determined on the basis of an extensive analysis of the NMR and MS data, and the absolute configurations were established by ECD calculations. Andrastone A (1) is a rare andrastin bearing an unusual cyclopentan-1,3-dione. It shows a selectively antiproliferative effect against HepG2 tumor cells with an IC50 value of 7.8 µM. Mechanism study showed that apoptosis via Caspase and RXRα pathways are responsible for the inhibitory effect.

A New Pimarane Diterpenoid from the Botryotinia fuckeliana Fungus Isolated from Deep-Sea Water.

A new pimarane diterpenoid, named botryopimarene A (1), was discovered from the fungus Botryotinia fuckeliana MCCC 3 A00494 isolated from the deep-sea water, together with ten known compounds. The planar structure of 1 was established based on the extensive spectroscopic analyses. The absolute configurations of tricyclic system in 1 were resolved by the theoretical ECD calculation, while the 15,16-diol moiety in the side chain was resolved by the Mo2 (OAc)4 -induced ECD spectrum. Compound 1, featuring a Δ9(11) double bond, was rarely discovered in pimarane family. Compounds 1-11 were tested for their cytotoxic activities using six human cancer cell lines by the MTT method. However, none of the compounds exhibited detectable cytotoxicities (IC50 >20 µm).

Penigrisacids A-D, Four New Sesquiterpenes from the Deep-Sea-Derived Penicillium griseofulvum.

Four new (penigrisacids A-D, 1-4) and one known (5) carotane sesquiterpenoids were isolated from the deep-sea-derived fungus Penicillium griseofulvum, along with four known compounds (6-9). The planar structures and relative configurations of the new compounds were determined by extensive analysis of the NMR and HRESIMS data. The absolute configurations were established by comparison of the experimental and calculated ECD (electronic circular dichroism) spectra or OR (optical rotation) value. Compound 9 exhibited potent anti-food allergic activity with IC50 value of 28.7 µM, while 4 showed weak cytotoxicity against ECA-109 tumor cells (IC50 = 28.7 µM).

Nesteretal A, A Novel Class of Cage-Like Polyketide from Marine-Derived Actinomycete Nesterenkonia halobia.

An intriguing cage-like polyhemiketal, nesteretal A (1), was isolated from the coral-derived actinomycete Nesterenkonia halobia. Its structure was established by extensive spectroscopic and computational methods. Nesteretal A is a highly oxygenated compound featuring an unprecedented 5/5/5/5 tetracyclic scaffold. A possible biosynthetic pathway of 1 from naturally occurring diacetyl was proposed. Compound 1 showed a weak retinoid X receptor-α (RXRα) transcriptional activation effect.

Aphidicolin Chemistry of the Deep-Sea-Derived Fungus Botryotinia fuckeliana MCCC 3A00494.

Aphidicolin, a potent DNA polymerase α inhibitor, has been explored in clinical trials for the treatment of cancer. So far, about 300 modified aphidicolins have been discovered. However, none have shown a stronger effect. Herein, we report 71 new (aphidicolins A1-A71, 1-71) and eight known (72-79) aphidicolin congeners from Botryotinia fuckeliana MCCC 3A00494, a fungus isolated from the western Pacific Ocean (-5572 m). The structures of 1-71 were determined through extensive spectroscopic analysis, X-ray crystallography, chemical derivatization, modified Mosher's method, and the ECD exciton chirality method. Compounds 54-57 and 58-64 are novel 6/6/5/6/5 pentacyclic aphidicolins featuring tetrahydrofuran and dihydrofuran rings, respectively, while compounds 65-71 are rare noraphidicolins. Aphidicolin A8 (8) significantly induced apoptosis in T24 (IC50 = 2.5 µM) and HL-60 (IC50 = 6.1 µM) cancer cells by causing DNA damage. By docking its structure to the human DNA polymerase α binding pocket, 8 was found to form tight intermolecular contacts, elaborating aphidicolin A8 as a potently cytotoxic lead compound.

Graphostromols A-K, Eleven New Chained Polyketides from the Deep-Sea-Derived Graphostroma sp.

Chromatographic separation of the AcOEt extract of the fermented cultures of the deep-sea-derived fungus Graphostroma sp. resulted in the isolation of 11 new chained polyketides, namely graphostromols A-K (1-11). The structures of the new compounds were established by the extensive analyses of their NMR and HR-ESI-MS data. The absolute configuration at C-11 in 1 was determined on the basis of the modified Mosher's method. Compounds 1-5, bearing a 2,2,10,10-tetramethyldodecane skeleton, were discovered for the first time from nature. All isolates were evaluated for their cytotoxicities against five different cancer cell lines (HeLa, Eca-109, Biu-87, Bel-7402, and PANC-1). However, none showed positive effects.

Sarocladione, a unique 5,10:8,9-diseco-steroid from the deep-sea-derived fungus Sarocladium kiliense.

A novel ergostane, sarocladione (1), was isolated from the deep-sea-derived fungus Sarocladium kiliense, along with 20 known compounds. The structure of 1 was determined mainly by a detailed analysis of its experimental and calculated NMR spectroscopic data. It is worth noting that 1 was the first steroid bearing a 5,10:8,9-diseco moiety. All 21 compounds were tested for in vitro antitumor activities against five cancer cell lines. ß-Sitostenone (7) and 4,6-dihydroxyeudesmane (20) showed significant effects on HeLa-S3 cells with the IC50 values of 9.2 µM and 9.3 µM, respectively.

Steroids from the Deep-Sea-Derived Fungus Penicillium granulatum MCCC 3A00475 Induced Apoptosis via Retinoid X Receptor (RXR)-α Pathway.

Five new ergostanes, penicisteroids D-H (1-5), were isolated from the liquid culture of the deep-sea-derived fungus Penicillium granulatum MCCC 3A00475, along with 27 known compounds. The structures of the new steroids were established mainly on the basis of extensive analysis of 1D and 2D NMR as well as HRESIMS data. Moreover, the absolute configurations of 1 were confirmed unambiguously by the single-crystal X-ray crystallography. Compounds 2 and 4⁻7 showed moderate antiproliferative effects selectively against 12 different cancer cell lines with IC50 values of around 5 µM. Compounds 2 and 6, potent RXRα binders with Kd values of 13.8 and 12.9 µM, respectively, could induce apoptosis by a Retinoid X Receptor (RXR)-α-dependent mechanism by regulating RXRα transcriptional expression and promoting the poly-ADP-ribose polymerase (PARP) cleavage. Moreover, they could inhibit proliferation by cell cycle arrest at the G0/G1 phase.

New anti-inflammatory guaianes from the Atlantic hydrotherm-derived fungus Graphostroma sp. MCCC 3A00421.

Nine new guaianes (graphostromanes A-I, 1-9) were isolated from the deep-sea-derived fungus Graphostroma sp. MCCC 3A00421, along with four known ones (10-13). The relative configurations were established mainly by detailed analysis of the NMR and HRESIMS data, while the absolute configurations were assigned using the X-ray crystallography and modified Mosher's method. All isolates were evaluated for their inhibitory effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages. Graphostromanes F (6) showed remarkable inhibitory effect with an IC50 value of 14.2 µM, which was even stronger than that of aminoguanidine, a positive control with an IC50 value of 23.4 µM.

Polyketides from the Deep-Sea-Derived Fungus Graphostroma sp. MCCC 3A00421 Showed Potent Antifood Allergic Activities.

To discover antifood allergic components from deep-sea-derived microorganisms, we performed a systematic chemical investigation of the Atlantic hydrothermal fungus Graphostroma sp. MCCC 3A00421. Consequently, nine new (1-9) and 19 known (10-28) polyketides were isolated. The planar structures of the new compounds were elucidated mainly by detailed analysis of their nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data, while the absolute configurations were established using the modified Mosher's method in association with electronic circular dichroism spectra. Graphostrin A (1) is a novel chlorinated polyketide derivate bearing an oxazole moiety. All isolates were tested for antifood allergic bioactivities in immunoglobulin E-mediated rat basophilic leukemia-2H3 cells. Reticulol (10) significantly decreased the rates of degranulation and histamine release with IC50 values of 13.5 and 13.7 µM, respectively, suggesting reticulol could be a potential antifood allergic medicine.

Saccharopolytide A, a new cyclic tetrapeptide with rare 4-hydroxy-proline moieties from the deep-sea derived actinomycete Saccharopolyspora cebuensis MCCC 1A09850.

A genome mining analysis on the deep-sea derived actinomycete Saccharopolyspora cebuensis MCCC 1A09850 indicated its potential to produce polypeptides. Accordingly, a systematic chemical investigation was conducted, which resulted in the isolation of one new cyclic tetrapeptide (saccharopolytide A, 1) and two known polyketides (2, 3) along with six other miscellaneous compounds (4‒9). Mainly by analysis of the 1D, 2D NMR and MS data, the chemical structure of saccharopolytide A was established as cyclo-(l-Leu-4-hydroxy-l-Pro-l-Phe-4-hydroxy-l-Pro). All isolates were evaluated for anti-allergic and anti-tumor bioactivities. Indol-3-carbaldehyde (4) showed weak anti-allergic effect with IC50 value of 55.75 µg/mL. And 2 showed weak anti-proliferative activity against Hela and H1299 tumor cell lines. Our results consolidate the potential of deep-sea-derived microorganisms to produce structurally interesting compounds.