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The article discusses the results of studies analyzing the bioactive constituents of marine-derived microorganisms. It details the discovery that a crude extract from a small-scale culture of the marine-mudflat-derived fungus Paecilomyces formosus displayed radical-scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and in vitro antimicrobial activity against methicillin- and multidrug-resistant Staphylococcus aureus (MRSA and MDRSA).

The fungus Chaetomium sp. is a causative agent of infections in humans and is ubiquitous in the natural environment. The secondary metabolites of this genus exhibit many biological activities, including antifungal activity and toxicity in mitochondria. In this study, we isolated cristazine from the fungus C. cristatum, which has the potential to inhibit the growth of human epidermoid carcinoma (A431) cells in a dose‐ and time‐dependent manner. Its inhibitory activity was examined using a cell viability assay and cell death was elucidated by western blot analysis. Cristazine triggered apoptotic cell death via the Type I death receptor pathway including the activation of caspases and other target proteins. However, cristazine did not have any effect on mitochondrial apoptotic proteins such as Bid, cytochrome c, and apoptosis‐inducing factor. Cristazine inhibited the cell cycle progression by arresting the G1/S phase and up‐regulating the inhibitory proteins of cyclin‐dependent kinases. Thus, cristazine has great potential for inducing apoptosis in A431 cells via both cell cycle arrest and the inhibition of cell growth. [ABSTRACT FROM AUTHOR]

Angiogenesis, the growth of new blood vessels from the existing ones, occurs during embryo development and wound healing. However, most malignant tumors require angiogenesis for their growth and metastasis as well. Therefore, inhibition of angiogenesis has been focused as a new strategy of cancer therapies. To treat cancer, there are marine microorganism-derived secondary metabolites developed as chemotherapeutic agents. In this study, we used toluhydroquinone (2-methyl-1,4-hydroquinone), one of the secondary metabolites isolated from marine algae symbiotic fungus, Aspergillus sp. We examined the effects of toluhydroquinone on angiogenesis using HUVECs. We identified that toluhydroquinone inhibited the activity of β-catenin and down-regulated Ras/Raf/MEK/ERK signaling which are crucial components during angiogenesis. In addition, the expression and activity of MMPs are reduced by the treatment of toluhydroquinone. In conclusion, we confirmed that toluhydroquinone has inhibitory effects on angiogenic behaviors of human endothelial cells, HUVECs. Our findings suggest that toluhydroquinone can be proposed as a potent anti-angiogenesis drug candidate to treat cancers. [ABSTRACT FROM AUTHOR]

The title compound, C13H14O3S, was prepared by the Lewis acid-catalysed reaction of 3-(4-hydroxy­phen­yl)propanoic acid with α-chloro-α-(methyl­sulfan­yl)acetone. The 1-benzofuran ring system is almost planar. The crystal structure is stabilized by aromatic π–π stacking inter­actions, H2C—H⋯π inter­actions and inversion-related inter­molecular O—H⋯O hydrogen bonds between the carboxyl groups. [ABSTRACT FROM AUTHOR]

The title compound, C11H12O2S, was prepared by the oxidation of 2,5-dimethyl-3-methyl­sulfanyl-1-benzofuran using 3-chloro­perbenzoic acid. The 1-benzofuran ring system is essentially planar. The crystal structure is stabilized by—CH2—H⋯π inter­actions. [ABSTRACT FROM AUTHOR]

The title compound, C19H14O2S, was prepared by the oxidation of 2-methyl-1-(phenyl­sulfan­yl)naphtho[2,1- b]furan using 3-chloro­perbenzoic acid. The naphthofuran ring system is approximately planar. The crystal structure is stabilized by inter­molecular aromatic π–π inter­actions between the furan and benzene rings. [ABSTRACT FROM AUTHOR]

The title compound, C15H16O2S2, was prepared by the Lewis acid-catalysed reaction of 2-methyl­resorcinol with α-chloro-α-(methyl­sulfan­yl)acetone. The benzo[1,2- b:5,4- b′]difuran group is almost planar. The crystal structure is stabilized by aromatic π–π stacking and —CH2—H⋯π inter­actions. [ABSTRACT FROM AUTHOR]

The title compound, C10H9ClO2S, was prepared by the oxidation of 5-chloro-2-methyl-3-methyl­sulfanyl-1-benzofuran using 3-chloro­perbenzoic acid. The benzofuran ring system is almost planar. No π–π or —CH2—H⋯π inter­actions were observed. [ABSTRACT FROM AUTHOR]

The title compound, C17H14O3S, was prepared by the Lewis acid-catalysed reaction of 4-hydroxy­phenyl­acetic acid with 2-chloro-2-(methyl­sulfan­yl)acetophenone. The 1-benzofuran ring system is nearly planar. The crystal structure is stabilized by aromatic π–π stacking inter­actions and inversion-related inter­molecular O—H⋯O hydrogen bonds between the carboxyl groups. [ABSTRACT FROM AUTHOR]

Abstract: Biological transformation of the bioactive sesquiterpene, cyclonerodiol (1), isolated from marine-derived fungus Myrothecium sp., was studied. Preparative-scale fermentation of 1 with marine-derived fungus Penicillium sp. resulted in the isolation of a new glycosidic metabolite, 7-O-(β-d-mannopyranosyl)cyclonerodiol (2). Fermentation of 1 for 2 weeks with a marine isolate of the actinomycete bacteria Streptomyces sp. also afforded two oxidized geometrical isomers, 10(Z)- and 10(E)-cyclonerotriols (3, 4). The stereostructure of the metabolites obtained was assigned on the basis of detailed spectroscopic data analyses and chemical reaction. [Copyright &y& Elsevier]

Abstract: Recently, mass mortality of adult flounder showing ascites occurred at many aquaculture farms in Korea. While we investigated the cause of the mortality, marine birnavirus (MABV-F) and bacteria (Vibrio harveyi and Edwardsiella tarda) were isolated from diseased fish. By the intraperitoneal (IP) injection with MABV-F, the virus strain did not show pathogenicity to the flounder. When the fish co-infected with MABV-F (IP) and V. harveyi or E. tarda (immersion), the cumulative mortality did not show any significant difference with control group. In contrast, the case of co-infection with MABV-F and bacteria by IP, cumulative mortality reached more than 90%. Most of the moribund and dead fish except for the mock-infected fish displayed ascites, and the virus and bacteria were re-isolated from all the dead and moribund fish except for the control fish. The results indicate that the cause of mass mortality of the adult fish may be due to bacterial infection. Higher mortalities may occur due to co-infection of MABV-F and bacteria, although MABV-F alone did not cause direct mortality. [Copyright &y& Elsevier]

The title compound, C16H12O4S, was prepared by oxidation of 5,6-methyl­enedi­oxy-3-methylsulfanylbenzofuran using m-chloro­perbenzoic acid. The 5,6-methyl­enedioxy­benzofuran ring system is approximately planar and the crystal structure involves aromatic π–π stacking. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve replacement is quickly becoming the standard of care for patients with severe aortic stenosis thanks to its minimally invasive nature and favorable outcomes. Recently, left ventricular pacing has been proposed as a safer alternative to traditional right heart pacing, which could simplify the transcatheter aortic valve replacement procedure overall, although procedural complications may still occur. This report describes a rare case of left ventricular pacing wire-induced acute severe mitral valve regurgitation during transcatheter aortic valve replacement., (© 2024 The Authors. Published by The Texas Heart Institute®.)

An 82-year-old woman was admitted for non-ST elevation myocardial infarction.

Hypoxia activates hypoxia-inducible factor 1, which promotes the progression of malignancy by stimulating angiogenesis and by augmenting the ability of tumors to survive. Thus, HIF-1 is one of the most compelling targets for treating cancers. The aim of this study was to find a small molecule that inhibits HIF-1 under hypoxia in cancer cells. 7,280 compounds in a chemical library were tested in a cancer cell line expressing luciferase HIF-dependently. Through three rounds of screening, we finally picked up a compound that originates from a marine bacterium parasitizing red alga. The antibiotic potently inhibited HIF-1 expression and its transcriptional activity in cancer cells exposed to hypoxia. Through two-step fractionation, diacetoxyscirpenol was purified and identified as a HIF-inhibiting ingredient. Mechanistically, diacetoxyscirpenol inhibits the synthesis of HIF-1α protein and also interferes with the dimerization of HIF-1α and ARNT. It attenuates HIF-mediated gene expression in cancer cells exposed to hypoxia, and by doing so reduces tumorigenic and angiogenic potentials of cancer cells. More importantly, diacetoxyscirpenol retarded tumor growth in mice, and reduced HIF-1α expression and vascular formation in the tumors. Overall, diacetoxyscirpenol is considered a potential drug deregulating the HIF-1 signaling pathway, and it could be beneficially employed for treating malignant tumors with hypoxic microenvironment., Competing Interests: The authors have no conflicts of interest to disclose.

The addition of metal bromides (NaBr and CaBr2) during fermentation of the marine-mudflat-derived fungus Aspergillus niger induced production of a new radical scavenging brominated naphthopyranone, 6,9-dibromoflavasperone (1); and three known naphtho-γ-pyranone monomers, flavasperone (2), TMC-256A1 (3), and fonsecin (4); and one naphtho-γ-pyranone dimer, aurasperone B (5). The structure of 6,9-dibromoflavasperone (1) was assigned through the combination of spectroscopic data analyses and comparison with the spectral data of flavasperone (2). Compounds 1-5 displayed potent radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl, with IC50 values of 21, 25, 0.3, 0.02, and 0.01 μM, respectively, and 3-5 were more potent than the positive control, ascorbic acid (IC50, 20.0 μM).

Cristazine (1), a new class of dioxopiperazine alkaloid, along with previously isolated chetomin (2), neoechinulin A (3), and golmaenone (4), were isolated from the mudflat-sediment-derived fungus Chaetomium cristatum. The structure and absolute stereochemistry of 1 was assigned on the basis of NMR, electron impact (EI)-MS, tandem FAB-MS/MS, and circular dichroism (CD) experiments. Compounds 1-4 displayed potent radical-scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), with IC50 values of 19, 15, 24, and 20 µM, respectively, which were similar to that of the positive control, ascorbic acid (IC50, 20 µM). Compound 1 also displayed cytotoxic activity against human cervical carcinoma (HeLa) cells, with an IC50 value of 0.5 µM.

Background: Epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase (RTK) family. Epidermal growth factor induces its dimerization and stimulates phosphorylation of intracellular tyrosine residues. Phosphorylation of EGFR is studied for cancer therapy because EGFR regulates many cellular processes including cell proliferation, differentiation, and survival. Hence, down-regulation of EGFR kinase activity results in inhibition of signaling cascades amenable for proliferation and progression of cell cycle., Methods: In the study, we purified 3,4-dihydroxyphenyl acetic acid and (+)-epoxydon from Aspergillus sp. isolated from marine brown alga Ishige okamurae and Phoma herbarum isolated from marine red alga Hypnea saidana respectively and determined its anti-tumor activities against HeLa human cervical cancer cells., Results: Two compounds suppressed EGFR activity in vitro with IC50 values for 3,4-dihydroxyphenyl acetic acid and (+)-epoxydon were 2.8 and 0.6 μg/mL respectively and reduced the viable numbers of HeLa cells. Immunoblotting analysis exhibited that the compounds induced inhibition of cell growth by causing downregulation of the mitogenic signaling cascade, inactivation of p90RSK, and release of cytochrome c from mitochondria., Conclusions: Results suggest that decreased expression of active EGFR and EGFR-related downstream molecules by treatment with the compounds may results in the inhibition of cell growth and inducement of apoptosis.

The addition of metal bromides (NaBr and CaBr2) during fermentation of a marine isolate of the fungus Aspergillus sp. induced production of two new brominated dihydroxyphenylacetic acid derivatives, methyl 2-(6-bromo-3,4-dihydroxyphenyl)acetate (1) and methyl 2-(2,5-dibromo-3,4-dihydroxyphenyl)acetate (2), and a known compound, 2-(3,4-dihydroxyphenyl)acetic acid (3). The structures of the two new compounds (1, 2) were assigned through the combination of spectroscopic data analyses and comparison with the spectral data of compound 3. Compounds 1-3 exhibited potent radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) with IC50 values (14.2, 12.1, 11.0 µm, respectively) demonstrating greater activity than the positive control (l-ascorbic acid; IC50, 20.0 µm).

In the title compound, C(21)H(13)FO(4)S·H(2)O, the dihedral angles between the mean plane of the benzofuran fragment (r.m.s. deviation = 0.005 Å) and the pendant 4-fluoro-phenyl and phenyl rings are 6.24 (7) and 83.39 (6)°, respectively. In the crystal, mol-ecules are linked by O-H⋯O and C-H⋯O hydrogen bonds.

The addition of NaBr to the fermentation medium of a marine isolate of the fungus Dothideomycete sp. resulted in induced production of two toluhydroquinone derivatives, 5- bromotoluhydroquinone (1) and 4-O-methyltoluhydroquinone (2), and two known compounds, toluhydroquinone (3) and gentisyl alcohol (4). The structures of 1 and 2 were assigned through the spectroscopic data analyses. Compounds 1-4 showed a potent antibacterial activity against the methicillinresistant and multidrug-resistant Staphylococcus aureus (MRSA and MDRSA) with MIC (minimum inhibitory concentration) values of 6.2, 12.5, 6.2, and 12.5 microgram/ml, respectively. Compounds 1-4 also exhibited a moderate radical scavenging activity against 1,1-diphenyl-2- picrylhydrazyl (DPPH) with IC(50) values of 11.0, 17.0, 12.0, and 7.0 microM, respectively, which were more active than the positive control, L-ascorbic acid (IC(50), 20.0 μM).

In the title compound, C(16)H(12)FIO(3)S, the 4-fluoro-phenyl ring makes a dihedral angle of 72.31 (6)° with the mean plane of the benzofuran fragment. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, and by an I⋯I contact [3.7764 (3) Å]. The crystal structure also exhibits a weak C-I⋯π [3.901 (3) Å] inter-action and a slipped π-π inter-action between the furan and benzene rings of neighbouring mol-ecules [centroid-centroid distance = 3.845 (3), inter-planar distance = 3.555 (3) and slippage = 1.465 (3) Å].

The title compound, C(13)H(13)BrO(3)S, was prepared by alkaline hydrolysis of ethyl 2-(5-bromo-3-isopropyl-sulfanyl-1-benzofuran-2-yl)acetate. In the crystal, the carboxyl groups are involved in inter-molecular O-H⋯O hydrogen bonds, which link the mol-ecules into dimers. These dimers are further packed into stacks along the c axis by inter-molecular C-H⋯π inter-actions, and by slipped π-π inter-actions between the furan rings of adjacent mol-ecules [centroid-centroid distance = 3.472 (2) Å, inter-planar distance = 3.398 (2) Å and slippage = 0.713 (2) Å].

In the title compound, C(18)H(15)FO(4)S, the fluoro-benzene ring makes a dihedral angle of 4.3 (1)° with the mean plane of the benzofuran fragment. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds. The O atom of the sulfinyl group is disordered over two orientations, with site-occupancy factors of 0.940 (3) and 0.060 (3).

In the title compound, C(17)H(15)FO(3)S, the 3-fluoro-phenyl ring makes a dihedral angle of 73.39 (4)° with the mean plane of the benzofuran fragment. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds. The crystal structure also exhibits a slipped π-π inter-action between the furan and benzene rings of neighboring mol-ecules [centroid-centroid distance = 3.743 (2) Å, inter-planar distance = 3.543 (2) Å and slippage = 1.207 (2) Å].

The title compound, C(13)H(13)FO(3)S, was prepared by alkaline hydrolysis of ethyl 2-(5-fluoro-3-isopropyl-sulfanyl-1-benzofuran-2-yl)acetate. In the crystal, the carb-oxy groups are involved in inter-molecular O-H⋯O hydrogen bonds, which link the mol-ecules into centrosymmetric dimers. These dimers are further packed into stacks along the b axis by a slipped π-π inter-action between the furan and benzene rings of neighbouring mol-ecules [centroid-centroid distance = 3.727 (2) Å, inter-planar distance = 3.465 (2) Å and slippage = 1.373 (2) Å]. The crystal structure also exhibits a short S⋯O contact [S⋯O = 3.219 (2) Å].

In the title compound, C(21)H(15)FOS, the dihedral angles between the mean plane of the benzofuran fragment and the pendant 3-fluoro-phenyl and phenyl rings are 1.76 (5) and 32.29 (5)°, respectively. In the crystal, mol-ecules are linked by a slipped π-π inter-action between the furan and benzene rings of neighbouring mol-ecules [centroid-centroid distance = 3.665 (2) Å, inter-planar distance = 3.391 (2) Å and slippage = 1.390 (2) Å].

In the title compound, C(21)H(15)FOS, the dihedral angle between the mean plane of the benzofuran fragment and the mean planes of the pendant 4-fluoro-benzene and phenyl rings are 31.72 (6)° and 32.51 (6)°, respectively. In the crystal, the mol-ecules are linked by weak C-H⋯π inter-actions. The crystal studied was a merohedral twin with a 0.62 (9):0.38 (9) domain ratio.

In the title molecule, C(16)H(13)ClO(3)S, the 3-chloro-phenyl ring makes a dihedral angle of 76.30 (5)° with the mean plane of the benzofuran fragment. In the crystal, pairs of inter-molecular C-H⋯π inter-actions link the mol-ecules into inversion dimers.

In the title compound, C(20)H(19)FO(2)S, the cyclo-pentyl ring adopts an envelope conformation. The 4-fluoro-phenyl ring makes a dihedral angle of 27.10 (7)° with the mean plane of the benzofuran fragment. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds and C-H⋯π inter-actions. In the cyclo-pentyl ring, one C atom is disordered over two orientations with site-occupancy factors of 0.617 (7) and 0.383 (7).

In the title compound, C(14)H(15)ClO(3)S, the cyclo-penyl ring adopts an envelope conformation. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds into dual chains propagating in [100]. The dual chains arise from pairs of the same or different hydrogen bonds between adjacent molecules.

In the title compound, C(24)H(15)FO(2)S, the 4-fluoro-phenyl ring makes a dihedral angle of 19.43 (4)° with the mean plane of the naphtho-furan fragment. The dihedral angle between the phenyl ring and the mean plane of the naphtho-furan fragment is 85.83 (4)°. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds.

In the title compound, C(18)H(24)O(3)S, the cyclo-hexyl ring adopts a chair conformation. In the crystal, mol-ecules are linked through weak inter-molecular C-H⋯O hydrogen bonds and C-H⋯π inter-actions. In the propyl group, one C atom is disordered over two sites with site-occupancy factors of 0.546 (8) and 0.454 (8).

In the title compound, C(18)H(17)FO(2)S, the 3-fluoro-phenyl ring makes a dihedral angle of 78.60 (5)° with the mean plane of the benzofuran fragment. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds and weak inter-molecular C-S⋯π [3.490 (2) Å] inter-actions.

In the title compound, C(16)H(13)FO(2)S, the 4-fluoro-phenyl ring makes a dihedral angle of 38.75 (8)° with the mean plane of the benzofuran fragment. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds.

In the title compound, C(20)H(12)BrFO(2)S, the 4-fluoro-phenyl ring makes a dihedral angle of 2.63 (6)° with the mean plane of the benzofuran fragment. The dihedral angle between the phenyl ring and the mean plane of the benzofuran fragment is 84.60 (6)°. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds, and slipped π-π inter-actions between the benzene rings of neighbouring mol-ecules [centroid-centroid distance = 3.719 (3) Å, inter-planar distance = 3.000 (3) Å and slippage = 1.520 (3) Å].

In the title compound, C(20)H(20)O(3)S, the cyclo-pentyl ring adopts an envelope conformation. The phenyl ring makes a dihedral angle of 81.40 (6)° with the mean plane of the benzofuran fragment. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds and C-H⋯π inter-actions.

In the title compound, C(19)H(24)O(4)S, the cyclo-hexyl ring adopts a chair conformation. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds. The O atom of the sulfinyl group is disordered over two orientations with site-occupancy factors of 0.875 (4) and 0.125 (4).

In the title compound, C(17)H(20)O(3)S, the cyclo-hexyl ring adopts a chair conformation. In the crystal, the carboxyl groups are involved in inter-molecular O-H⋯O hydrogen bonds, which link the mol-ecules into centrosymmetric dimers. These dimers are further stabilized by weak inter-molecular C-H⋯O hydrogen bonds. In addition, the crystal structure also exhibits aromatic π-π inter-actions between the furan rings of adjacent mol-ecules [centroid-centroid distance = 3.505 (2) Å, inter-planar distance = 3.385 (2) Å and slippage = 0.909 (2) Å], and inter-molecular C-H⋯π inter-actions.

In the title compound, C(16)H(19)IO(3)S, the cyclo-hexyl ring adopts a chair conformation. In the crystal, pairs of inter-molecular I⋯O contacts [3.269 (2) Å] link the mol-ecules into inversion dimers. These dimers are further stabilized by a slipped π-π inter-action between the benzene and furan rings of adjacent mol-ecules [centroid-centroid distance = 3.701 (3) Å, inter-planar distance = 3.372 (3) Å and slippage = 1.525 (3) Å].

The title compound, C(12)H(11)FO(3)S, was prepared by alkaline hydrolysis of ethyl 2-(5-fluoro-7-methyl-3-methyl-sulfanyl-1-benzofuran-2-yl)acetate. In the crystal, the carboxyl groups are involved in inter-molecular O-H⋯O hydrogen bonds, which link the mol-ecules into centrosymmetric dimers.

There are two independent mol-ecules, A and B, in the asymmetric unit of the title compound, C(14)H(15)FO(3)S, in each of which the cyclo-pentyl ring adopts an envelope conformation. The benzofuran units in each mol-ecule are essentially planar, with mean deviations from the least-squares plane defined by the nine constituent ring atoms of 0.009 (2) Å for mol-ecule A and 0.013 (2) Å for mol-ecule B. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds. In the cyclo-pentyl ring of mol-ecule B, one C atom is disordered over two positions with site-occupancy factors of 0.60 (2) and 0.40 (2).