Reisolation and Structure Revision of Asperspiropene A.

Asperspiropene A was originally reported to have a unique 1,8-dioxaspiro[4.5]decane skeleton. During the course of our ongoing research for novel marine natural products, we isolated compound 1, which has identical 1D and 2D NMR data to asperspiropene A. Detailed and careful analysis of spectroscopic data led us to revise the structure of asperspiropene A and to determine its absolute configuration.

Two New Phomaligols from the Marine-Derived Fungus Aspergillus flocculosus and Their Anti-Neuroinflammatory Activity in BV-2 Microglial Cells.

Two new phomaligols, deketo-phomaligol A (1) and phomaligol E (2), together with six known compounds (3-8) were isolated from the culture broth of the marine-derived fungus Aspergillus flocculosus. Compound 1 was first isolated as a phomaligol derivative possessing a five-membered ring. The structures and absolute configurations of the new phomaligols were determined by detailed analyses of mass spectrometry (MS), nuclear magnetic resonance (NMR) data, optical rotation values and electronic circular dichroism (ECD). In addition, the absolute configurations of the known compounds 3 and 4 were confirmed by chemical oxidation and comparison of optical rotation values. Isolated compounds at a concentration of 100 µM were screened for inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells. Among the compounds, 4 showed moderate anti-neuroinflammatory effects with an IC50 value of 56.6 µM by suppressing the production of pro-inflammatory mediators in activated microglial cells without cytotoxicity.

Polyketides and Meroterpenes from the Marine-Derived Fungi Aspergillus unguis 158SC-067 and A. flocculosus 01NT-1.1.5 and Their Cytotoxic and Antioxidant Activities.

Ten secondary metabolites, including a new grifolin analog, grifolin B (1); a new homovalencic acid derivative, 12-hydroxyhomovalencic acid (7); and a compound isolated from a natural source for the first time (9), along with seven known compounds, grifolin (2), averantin (3), 7-chloroaverantin (4), 1'-O-methylaverantin (5), 7-hydroxy-2-(2-hydroxypropyl)-5-pentylchromone (6), homovalencic acid (8), and bekeleylactone E (10), were isolated from two fungal strains. The structures of 1-10 were identified by detailed analysis and comparison of their spectroscopic data with literature values. Compounds 9 and 10 showed moderate cytotoxic activity against a panel of cancer cell lines (PC-3, HCT-15, MDA-MB-231, ACHN, NCI-H23, NUGC-3), with the GI50 values ranging from 1.1 µM to 3.6 µM, whereas 1 displayed a weak 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity without cytotoxicity against all tested cell lines.

New Polyenes from the Marine-Derived Fungus Talaromyces cyanescens with Anti-Neuroinflammatory and Cytotoxic Activities.

Three new polyene compounds, talacyanols A-C (1-3), along with two known compounds, ramulosin (4) and eurothiocin A (5), were isolated from the marine fungus Talaromyces cyanescens derived from a seaweed Caulerpa sp. Structures of 1-5 were established by one-dimensional and two-dimensional (1D/2D) NMR, HR-ESIMS, and the modified Mosher's methods, as well as comparison with previously reported literature data. All the compounds (1-5) were tested for their in vitro cytotoxic and anti-neuroinflammatory activities. Among them, 1 showed moderate cytotoxic activity against a panel of cancer cell lines (HCT-15, NUGC-3, NCI-H23, ACHN, PC-3, and MDA-MB-231) with GI50 values ranging from 44.4 to 91.6 µM, whereas compounds 2 and 5 exhibited anti-neuroinflammatory effect without cytotoxicity against all the tested cell lines.

Insight into Antioxidant and Photoprotective Properties of Natural Compounds from Marine Fungus.

This computational and experimental work aims to elucidate physicochemical and photophysical natures of free radical scavenging and ultraviolet radiation (UVR) filtering activities of five terpenoids available in the extract of marine fungus. The antioxidant activities of ochraceopone F (C1), aspertetranone D (C2), cycloechinulin (C3), wasabidienone E (C4), and mactanamide (C5) are evaluated by using density functional theory (DFT) at the M05-2X/6-311++G(d,p) level of theory in the gas phase, water, and pentyl ethanoate (PEA). Double antioxidant mechanisms allowing the second (H+/e-) donation such as double hydrogen atom transfer (dHAT), double single electron transfer-proton transfer (dSET-PT), and double sequential proton loss-electron transfer (dSPL-ET) are considered. Reaction enthalpies (ΔrH0), standard Gibbs free energies (ΔrG0) and potential energy surfaces of reactions toward HOO• radical are then established to evaluate the hydrogen transfer (HT) and radical adduct formation (RAF) mechanisms. The computational results are supported by DPPH• and ABTS•+ antioxidant essays. Results show that all compounds C1-C5 are able to scavenge two free radicals via dHAT, dSET-PT, and dSPL-ET mechanisms. Among the compounds, C3 and C4 represent the most potential antioxidants, especially via HAT and RAF mechanisms in all the reaction media. Their rate constants for both HAT and RAF reactions are remarkably higher than that of Trolox and ascorbic acid. The kinetic calculations on activation Gibbs free energies (ΔG⧧) and rate constants (kTST) based on conventional transition state theory (TST) reveal that HAT and RAF processes are in competition in solvents. Photophysical processes occurring during UVR exposure are investigated using the time dependent density functional theory (TD-DFT) combined with UV-vis experiments. The obtained results highlight the promising activities of C1-C5 in UVR absorption in the ranges of UVA and UVB. Among them, C3 and C4 also show better UV absorption properties with the easiest excitations (band gaps equal to 4.06 and 3.65 eV). This study suggests the natural candidates possibly used in organic sunscreen.

Anti-Neuroinflammatory Agent, Restricticin B, from the Marine-Derived Fungus Penicillium janthinellum and Its Inhibitory Activity on the NO Production in BV-2 Microglia Cells.

A new compound containing a triene, a tetrahydropyran ring and glycine ester functionalities, restricticin B (1), together with four known compounds (2-5) were obtained from the EtOAc extract of the marine-derived fungus Penicillium janthinellum. The planar structure of 1 was determined by detailed analyses of MS, 1D and 2D NMR data. The relative and absolute configurations of 1 were established via the analyses of NOESY spectroscopy data, the comparison of optical rotation values with those of reported restricticin derivatives and electronic circular dichroism (ECD). All the compounds were screened for their anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced BV-2 microglia cells. Restricticin B (1) and N-acetyl restricticin (2) exhibited anti-neuroinflammatory effects by suppressing the production of pro-inflammatory mediators in activated microglial cells.

Resorcinosides A and B, Glycosylated Alkylresorcinols from a Marine-Derived Strain of the Fungus Penicillium janthinellum.

Two new glycosylated alkylresorcinols, resorcinosides A (1) and B (2), were isolated from a strain of the fungus Penicillium janthinellum derived from a marine sediment sample collected from Cu Lao Cham Island, Vietnam. The structures of 1 and 2 were established by interpretation of 1D and 2D NMR and high-resolution ESIMS data, and their absolute configurations were confirmed by the coupling constant of the anomeric proton, acid hydrolysis, subsequent HPLC analysis, Mosher's method, and quantum-mechanics-based computational analysis of NMR chemical shifts. The structure elucidation indicated that 1 and 2 are new alkylresorcinols with d-glucose, and 2 has an α-pyrone moiety attached to the aromatic ring. Compound 1 exhibited cytotoxic activity against the NUGC-3 cancer cell line with a GI50 value of 9.3 µM.

Dokdolipids A-C, Hydroxylated Rhamnolipids from the Marine-Derived Actinomycete Actinoalloteichus hymeniacidonis.

Three new hydroxylated rhamnolipids, dokdolipids A-C (1-3) were obtained from the marine actinomycete Actinoalloteichus hymeniacidonis, which was isolated from a sediment sample collected off the coasts of Dokdo island, Republic of Korea. The structures of the isolated compounds were elucidated on the basis of 1D and 2D NMR and mass spectrometric data analyses. Their absolute configurations were assigned using the modified Mosher's method and specific rotation values, as well as acid hydrolysis, chemical derivatizations and subsequent HPLC analysis to determine the configuration of the sugar moieties. All new compounds were evaluated for their cytotoxicity against six cancer cell lines, HCT-15, NUGC-3, NCI-H23, ACHN, PC-3 and MDA-MB-231. Compounds 1-3 displayed moderate cytotoxicity against all the cell lines tested with IC50 values ranging from 13.7-41.5 µM.

Phenazine Derivatives with Anti-Inflammatory Activity from the Deep-Sea Sediment-Derived Yeast-Like Fungus Cystobasidium laryngis IV17-028.

Three new phenazine derivatives (1-3), along with known compounds (4-7) of saphenic acid derivatives, were isolated from a deep-sea sediment-derived yeast-like fungus Cystobasidium larynigs collected from the Indian Ocean. The structures of the new compounds (1-3) were determined by analysis of spectroscopic data, semi-synthesis and comparison of optical rotation values. All the isolated compounds (1-7), except for 2, showed nitric oxide (NO) production inhibitory effect against lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells without cytotoxicity at concentrations up to 30 µg/mL. This is the first report on the yeast-like fungus Cystobasidium laryngis producing phenazines and anti-inflammatory activity of 1-7 including saphenic acid (4).

New Ophiobolin Derivatives from the Marine Fungus Aspergillus flocculosus and Their Cytotoxicities against Cancer Cells.

Five new sesterterpenes, 14,15-dehydro-6-epi-ophiobolin K (1), 14,15-dehydro- ophiobolin K (2), 14,15-dehydro-6-epi-ophiobolin G (3), 14,15-dehydro-ophiobolin G (4) and 14,15-dehydro-(Z)-14-ophiobolin G (5), together with four known ophiobolins (6-9) were isolated from the marine fungus Aspergillus flocculosus derived from the seaweed Padina sp. collected in Vietnam. The five new ophiobolins were first isolated as ophiobolin derivatives consisting of a fully unsaturated side chain. Their structures were elucidated via spectroscopic methods including 1D, 2D NMR and HR-ESIMS. The absolute configurations were determined by the comparison of chemical shifts and optical rotation values with those of known ophiobolins. All compounds (1-9) were then evaluated for their cytotoxicity against six cancer cell lines, HCT-15, NUGC-3, NCI-H23, ACHN, PC-3 and MDA-MB-231. All the compounds showed potent cytotoxicity with GI50 values ranging from 0.14 to 2.01 µM.

Suppression of RANKL-Induced Osteoclastogenesis by the Metabolites from the Marine Fungus Aspergillus flocculosus Isolated from a Sponge Stylissa sp.

A new α-pyrone merosesquiterpenoid possessing an angular tetracyclic carbon skeleton, ochraceopone F (1), and four known secondary metabolites, aspertetranone D (2), cycloechinulin (3), wasabidienone E (4), and mactanamide (5), were isolated from the marine fungus Aspergillus flocculosus derived from a sponge Stylissa sp. collected in Vietnam. The structures of Compounds 1-5 were elucidated by analysis of 1D and 2D NMR spectra and MS data. All the isolated compounds were evaluated for anti-proliferation activity and their suppression effects on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation using tartate-resisant acid phosphatase (TRAP). Compounds 1-5 had no anti-proliferative effect on human cancer cell lines up to 30 µg/mL. Among these compounds, aspertetranone D (2) and wasabidienone E (4) exhibited weak osteoclast differentiation inhibitory activity at 10 µg/mL. However, mactanamide (5) showed a potent suppression effect of osteoclast differentiation without any evidence of cytotoxicity.

Streptoglycerides A-D with a Rare 6/5/5 Tricyclic Ring Skeleton from a Marine Actinomycete Streptomyces species.

Four novel secondary metabolites possessing a unique 6/5/5 tricyclic ring system, streptoglycerides A-D (1-4), were isolated from a marine actinomycete Streptomyces sp. derived from a mangrove sample collected on Kosrae Island. Their structures and absolute configurations were elucidated by spectroscopic data and electronic circular dichroism data. Streptoglyceride C (3) showed a weak inhibitory effect on the production of nitric oxide in BV-2 microglia cells.