Differentiation-Promoting Effects of Okeaniamides A and B from an Okeania sp. Marine Cyanobacterium on Preadipocytes.

The linear lipopeptides okeaniamide A (1) and okeaniamide B (2) were isolated from an Okeania sp. marine cyanobacterium collected in Okinawa. The structures of these compounds were established by spectroscopic analyses, and the absolute configurations were elucidated based on a combination of chemical degradations, Marfey's analysis, and derivatization reactions. Okeaniamide A (1) and okeaniamide B (2) dose-dependently promoted the differentiation of mouse 3T3-L1 preadipocytes in the presence of insulin.

Studies on the Catechin Constituents of Bark of Cinnamomum sieboldii.

Screening for bioactivity related to anti-infective, anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-viral activity, led us to identify active compounds from a methanol extract of Litsea japonica (Thub.) Juss. and the hot water extract of bark of Cinnamomum sieboldii Meisn (also known as Karaki or Okinawa cinnamon). The two main components in these extracts were identified as the catechin trimers (+)-cinnamtannin B1 and pavetannin B5. Moreover, these extracts exhibited anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity. The structures of these catechin trimers were previously determined by chemical and spectroscopic methods. Pavetanin B5 has never been reported to be isolated as a pure form and has been obtained as a mixture with another component. Although other groups have reported the putative structure of pavetannin B5, preparation of the methylated derivative of pavetannin B5 in this study allowed us to obtain the pure form for the first time as the undecamethyl derivative and confirm its exact structure. Commercially available (+)-cinnamtannin B1 and aesculitannin B (C2'-epimer of cinnamtannin B1) both of which contained pavetannin B5 as a minor component, and C. sieboldii bark extract (approx. 5/2 mixture of (+)-cinnamtannin B1/pavetannin B5) were assessed for anti-SARS-CoV-2 activity. Both C. sieboldii bark extract and commercially available aesculitannin B showed viral growth inhibitory activity.

A new isomaneonene derivative from the red alga Laurencia cf. mariannensis.

Determining the structures of new natural products from marine species not only enriches our understanding of the diverse chemistry of these species, but can also lead to the discovery of compounds with novel and/or important biological activities. Herein, we describe the isolation of isomaneonene C (1), a new halogenated C15 acetogenin, and three known compounds, α-snyderol (2), cis-maneonene D (3), and isomaneonene B (4), from the organic extract obtained from the red alga Laurencia cf. mariannensis collected from Iheya Island, Okinawa, Japan. The structures of these secondary metabolites were elucidated spectroscopically. All compounds were inactive at 30 µg/disc against methicillin-resistant Staphylococcus aureus (MRSA) in combination treatment with a ß-lactam drug, meropenem.

Identification of four allelopathic compounds including a novel compound from Elaeocarpus floribundus Blume and determination of their allelopathic activity.

Allelopathic compounds can play a vital role in protecting the environment from pollution by synthetic herbicides. Compounds isolated from plant species with allelopathic potential can be used as natural herbicides to control weeds and help reduce environmental pollution. Elaeocarpus floribundus has been reported to contain allelopathic compounds. Aqueous methanolic extracts of the leaves of this plant showed strong growth inhibitory potential against two test species (monocotyledonous Italian ryegrass and dicotyledonous alfalfa) in plants- and dose-dependent technique. Several extensive chromatographic separations of the E. floribundus leaf extracts yielded four active compounds 1, 2, 3, and 4 (novel compound). All the identified compounds showed strong growth inhibitory potential against cress. The concentrations caused for 50% growth limitation (I50 values) of the cress seedlings were in the range 500.4-1913.1 µM. The findings indicate that the identified compounds might play a pivotal function in the allelopathic potential of E. floribundus tree. This report is the first on elaeocarpunone and its allelopathic potential.

Odookeanynes A and B, Acetylene-Containing Lipopeptides from an Okeania sp. Marine Cyanobacterium.

Odookeanynes A (1) and B (2), two acetylene-containing lipopeptides, were isolated from an Okeania sp. marine cyanobacterium collected in Okinawa, Japan. Their structures were elucidated by spectroscopic analysis and Marfey's analysis of acid hydrolysates. Odookeanynes A (1) and B (2) dose-dependently promoted the differentiation of mouse 3T3-L1 preadipocytes in the presence of insulin.

Koshidacins A and B, Antiplasmodial Cyclic Tetrapeptides from the Okinawan Fungus Pochonia boninensis FKR-0564.

Two new antiplasmodial peptides, named koshidacins A (1) and B (2), were discovered from the culture broth of the Okinawan fungus Pochonia boninensis FKR-0564. Their structures, including absolute configurations, were elucidated by a combination of spectroscopic methods and chemical derivatization. Both compounds showed moderate in vitro antiplasmodial activity against Plasmodium falciparum strains, with IC50 values ranging from 17.1 to 0.83 µM. In addition, compound 2 suppressed 41% of malaria parasites in vivo when administered intraperitoneally at a dose of 30 mg/kg/day for 4 days.

Effect of methoxyflavones contained in Kaempferia parviflora on CRE-mediated transcription in PC12D cells.

The cAMP-response element (CRE) is critical in the formation of long-term memory. To prove the pharmacological effects of the methoxyflavones-rich residue (MRR) and its constituent methoxyflavones (1-9) extracted from the rhizomes of Kaempferia parviflora on the nervous system, we examined the effects of the MRR and methoxyflavones (1-9) on CRE-mediated transcription in PC12D cells. The MRR increased CRE-mediated transcription in PC12D cells. In addition, among methoxyflavones (1-9) isolated from MRR, compounds 1-4 increased CRE-mediated transcription. These results suggest that K. parviflora and methoxyflavone might be very useful materials for preventing and recovering from cognitive decline.

Structure-Activity Relationship Study of Majusculamides A and B and Their Analogues on Osteogenic Activity.

We discovered that majusculamide A (1) and majusculamide B (2), isolated from a marine cyanobacterium collected in Okinawa, induced osteoblast differentiation in MC3T3-E1 cells. Although majusculamide A (1) has a different configuration only at the C-19 stereocenter, bearing a methyl group, compared to majusculamide B (2), the effect of 1 was stronger than that of 2. We synthesized some analogues of the majusculamides (3-15) and evaluated osteogenic activities of these analogues. The structure-activity relationship study of majusculamide analogues suggested that the number of methyls and configuration at C-19 and the nature of the substituent at C-20 of majusculamide A (1) may be important for the osteoblast differentiation-inducing effect of 1.

Irijimasides A-E, Macrolide Glycosides from an Okeania sp. Marine Cyanobacterium.

Irijimasides A-E (1-5), a series of new 14-membered macrolide glycosides, were isolated from a marine cyanobacterium collected in Okinawa. The gross structures of 1-5 were established by spectroscopic analysis, including 2D NMR, while absolute stereostructures were determined based on NOESY spectra, chemical derivatization, and ECD data. All five macrolides suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP) activity in mouse RAW264 macrophage cells, indicating that these compounds inhibit osteoclast formation.

Potential use of Schumannianthus dichotomus waste: the phytotoxic activity of the waste and its identified compounds.

The phytotoxic potential of the leaves and twigs of Schumannianthus dichotomus, discarded in the mat-making industry against four test plants (lettuce (Lactuca sativa L.), rapeseed (Brassica napus L.), foxtail fescue (Vulpia myuros (L.) C.C. Gmel.) and timothy (Phleum pratense L.)) was investigated and found strong phytotoxic activity. An assay-guided fractionation of S. dichotomus extarcts against cress (Lepidium sativum L.) through a series of column chromatography steps yielded two compounds, 8-(5-oxo-2,5-dihydrofuran-2-yl) octanoic acid (ODFO) and (E)-6-hydroxy-2,6-dimethylocta-2,7-dienoic acid (8-carboxylinalool). ODFO and 8-carboxylinalool showed strong phytotoxic activity against cress and timothy. The concentrations required for 50% growth inhibition (I50 value) of the seedlings of cress and timothy were 111.94-128.01 and 36.30-91.75 µM, respectively, for ODFO, but the values were much higher at 315.98-379.13 and 107.92-148.41 µM, respectively, for 8-carboxylinalool, indicating the stronger phytotoxic activity of ODFO. This study is the first to isolate ODFO and 8-carboxylinalool from S. dichotomus and their phytotoxic potential while ODFO is firstly encountered from any natural source. The growth inhibitory activity of the identified compounds may explain their role in the phytotoxic activity of S. dichotomus, which suggests the possible use of its leaves and twigs or its active constituents as natural bioherbicides.

Isolation and Total Synthesis of Mabuniamide, a Lipopeptide from an Okeania sp. Marine Cyanobacterium.

The bioassay-guided fractionation of an Okeania sp. marine cyanobacterium collected in Okinawa led to the isolation of the lipopeptide mabuniamide (1). The gross structure of 1 was determined by spectroscopic analyses, and its absolute configuration was determined using Marfey's analysis of the acid hydrolysate of 1. The absolute configuration of 1 was confirmed by total synthesis. Mabuniamide (1) stimulated glucose uptake in cultured rat L6 myotubes. In addition, mabuniamide (1) and its stereoisomer (2) exhibited moderate antimalarial activity.

Isolation of Jahanene and Jahanane, and Total Synthesis of the Jahanyne Family.

Two new jahanyne analogues, jahanene and jahanane, highly N-methylated lipopeptides, were isolated from a marine cyanobacterium Okeania sp., and their structures were determined by NMR and MS. In addition, we achieved total syntheses of the jahanyne family and assessed their activities. The resulting growth-inhibitory activity of jahanyne was nearly one-tenth of the previously reported activity. Furthermore, we found that the degree of unsaturation at the terminus of the fatty acid moiety affected the growth-inhibitory activity against human cancer cells.

Ypaoamides B and C, Linear Lipopeptides from an Okeania sp. Marine Cyanobacterium.

Two new pyrrolinone-containing lipopeptides, ypaoamides B (1) and C (2), were isolated from an Okeania sp. marine cyanobacterium collected in Okinawa. Their structures were determined by spectroscopic analysis and Marfey's analysis of acid hydrolysates. Ypaoamides B (1) and C (2) stimulated glucose uptake in cultured rat L6 myotubes. In particular, ypaoamide B (1) showed potent activity and activated AMP-activated protein kinase.

Leptolyngbyolides, Cytotoxic Macrolides from the Marine Cyanobacterium Leptolyngbya sp.: Isolation, Biological Activity, and Catalytic Asymmetric Total Synthesis.

Four new macrolactones, leptolyngbyolides A-D, were isolated from the cyanobacterium Leptolyngbya sp. collected in Okinawa, Japan. The planar structures of leptolyngbyolides were determined by extensive NMR studies, although complete assignment of the absolute configuration awaited the catalytic asymmetric total synthesis of leptolyngbyolide C. The synthesis took advantage of the catalytic asymmetric thioamide-aldol reaction using copper(I) complexed with a chiral bidentate phosphine ligand to regulate two key stereochemistries of the molecule at the outset. The present total synthesis demonstrates the utility of this reaction for the construction of complex chemical entities. In addition to the total synthesis, this work reports that leptolyngbyolides depolymerize filamentous actin (F-actin) both in vitro and in cells. Detailed biological studies suggest the probable order of F-actin depolymerization and apoptosis caused by leptolyngbyolides.

Biseokeaniamides A, B, and C, Sterol O-Acyltransferase Inhibitors from an Okeania sp. Marine Cyanobacterium.

Biseokeaniamides A, B, and C (1-3), structurally novel sterol O-acyltransferase (SOAT) inhibitors, were isolated from an Okeania sp. marine cyanobacterium. Their structures were elucidated by spectroscopic analyses and degradation reactions. Biseokeaniamide B (2) exhibited moderate cytotoxicity against human HeLa cancer cells, and compounds 1-3 inhibited both SOAT1 and SOAT2, not only at an enzyme level but also at a cellular level. Biseokeaniamides (1-3) are the first linear lipopeptides that have been shown to exhibit SOAT-inhibitory activity.

Three New Malyngamides from the Marine Cyanobacterium Moorea producens.

Three new compounds of the malyngamide series, 6,8-di-O-acetylmalyngamide 2 (1), 6-O-acetylmalyngamide 2 (2), and N-demethyl-isomalyngamide I (3), were isolated from the marine cyanobacterium Moorea producens. Their structures were determined by spectroscopic analysis and chemical derivatization and degradation. These compounds stimulated glucose uptake in cultured L6 myotubes. In particular, 6,8-di-O-acetylmalyngamide 2 (1) showed potent activity and activated adenosine monophosphate-activated protein kinase (AMPK).

Total synthesis of odoamide, a novel cyclic depsipeptide, from an Okinawan marine cyanobacterium.

Odoamide is a novel cyclic depsipeptide with highly potent cytotoxic activity isolated from the Okinawan marine cyanobacterium Okeania sp. It contains a 26-membered macrocycle composed of a fatty acid moiety, a peptide segment and isoleucic acid. Four possible stereoisomers of the odoamide polyketide substructure were synthesised using a chiral pool approach. The first total synthesis of odoamide was also successfully achieved. The structure of synthetic odoamide was verified by comparing its NMR spectra with those of the natural product.

Isolation and Identification of Allelopathic Substances from Forsythia suspensa Leaves, and Their Metabolism and Activity.

The fruit of Forsythia suspensa (Thunb.) Vahl has been used in traditional Chinese medicine as "Forsythiae fructus". The species is also grown in parks and gardens, and on streets and building lots, as an ornamental plant, but it requires pruning. In this study, the allelopathic activity and allelopathic substances in the leaves of pruned branches of F. suspensa were investigated to determine any potential application. The leaf extracts of F. suspensa showed growth inhibitory activity against three weed species; Echinochloa crus-galli, Lolium multiflorum, and Vulpia myuros. Two allelopathic substances in the extracts were isolated through the bioassay-guided purification process, and identified as (-)-matairesinol and (-)-arctigenin. (-)-Matairesinol and (-)-arctigenin, which showed significant growth inhibitory activity at concentrations greater than 0.3 mM in vitro. The inhibitory activity of (-)-arctigenin was greater than that of (-)-matairesinol. However, both compounds were more active than (+)-pinolesinol which is their precursor in the biosynthetic pathway. The investigation suggests that F. suspensa leaves are allelopathic, and (-)-matairesinol and (-)-arctigenin may contribute to the growth inhibitory activities. Therefore, the leaves of the pruned branches can be applied as a weed management strategy in some agricultural practices such as using the leaf extracts in a foliar spray and the leaves in a soil mixture, thereby reducing the dependency on synthetic herbicides in the crop cultivation and contributing to developing eco-friendly agriculture.

Allelopathy and Identification of Five Allelochemicals in the Leaves of the Aromatic Medicinal Tree Aegle marmelos (L.) Correa.

Aegle marmelos (L.) Correa is an economically and therapeutically valuable tree. It is cultivated as a fruit plant in southeast Asian countries. In this research, we investigated the allelopathy and possible allelochemicals in the leaves of A. marmelos. Aqueous methanol extracts of A. marmelos exhibited significant inhibitory effects against the growth of Lepidium sativum, Lactuca sativa, Medicago sativa, Echinochloa crusgalli, Lolium multiflorum, and Phleum pratense. Bioassay-directed chromatographic purification of the A. marmelos extracts resulted in identifying five active compounds: umbelliferone (1), trans-ferulic acid (2), (E)-4-hydroxycinnamic acid methyl ester (3), trans-cinnamic acid (4), and methyl (E)-3'-hydroxyl-4'-methoxycinnamate (5). The hypocotyl and root growth of L. sativum were considerably suppressed by these compounds. Methyl (E)-3'-hydroxyl-4'-methoxycinnamate also suppressed the coleoptile and root growth of E. crusgalli. The concentrations of these compounds, causing 50% growth reduction (I50) of L. sativum, were in the range of 74.19-785.4 µM. The findings suggest that these isolated compounds might function in the allelopathy of A. marmelos.

Synergistic effect of secondary metabolites isolated from Pestalotiopsis sp. FKR-0115 in overcoming ß-lactam resistance in MRSA.

Six aromatic secondary metabolites, pestalone (1), emodin (2), phomopsilactone (3), pestalachlorides B (4), C (5), and D (6), were isolated from Pestalotiopsis sp. FKR-0115, a filamentous fungus collected from white moulds growing on dead branches in Minami Daito Island. The efficacy of these secondary metabolites against methicillin-resistant Staphylococcus aureus (MRSA) with and without meropenem (ß-lactam antibiotic) was evaluated using the paper disc method and broth microdilution method. The chemical structures of the isolated compounds (1-6) were characterised using spectroscopic methods, including nuclear magnetic resonance and mass spectrometry. All six isolated compounds exhibited synergistic activity with meropenem against MRSA. Among the six secondary metabolites, pestalone (1) overcame bacterial resistance in MRSA to the greatest extent.