Arihiro Iwasaki

Jahanyne, an apoptosis-inducing lipopeptide from the marine cyanobacterium Lyngbya sp.

An acetylene-containing lipopeptide, jahanyne, was isolated from the marine cyanobacterium Lyngbya sp. Its gross structure was established by spectroscopic analyses, and the absolute configuration was clarified based on a combination of chiral HPLC analyses, spectroscopic analyses, and derivatization reactions. Jahanyne significantly inhibited the growth of human cancer cells and induced apoptosis in HeLa cells.

Isolation and Structure of Kurahyne B and Total Synthesis of the Kurahynes

Kurahyne B (2), a new analogue of kurahyne (1), was isolated from the marine cyanobacterium Okeania sp. Its gross structure was elucidated based on spectroscopic analyses, and the absolute configuration was established by total synthesis. Kurahyne B (2) inhibited the growth of both HeLa and HL60 cells, with IC50 values of 8.1 and 9.0 μM, respectively. The growth-inhibitory activity of kurahyne B was the same as kurahyne (1). In parallel, the first total synthesis of kurahyne (1) was also achieved.

Janadolide, a Cyclic Polyketide-Peptide Hybrid Possessing a tert-Butyl Group from an Okeania sp. Marine Cyanobacterium.

Janadolide, a new cyclic polyketide-peptide hybrid possessing a tert-butyl group, was isolated from an Okeania sp. marine cyanobacterium. The gross structure was elucidated by spectroscopic analyses, and the absolute configurations of the amino acid moieties were determined by acid hydrolysis and chiral-phase HPLC analyses. The absolute configuration of the two stereogenic centers in the polyketide moiety was elucidated based on a combination of degradation reactions and spectroscopic analyses including the phenyl-glycine methyl ester method. Janadolide showed potent antitrypanosomal activity with an IC50 value of 47 nM without cytotoxicity against human cells at 10 μM.

Kurahyne, an acetylene-containing lipopeptide from a marine cyanobacterial assemblage of Lyngbya sp.

Kurahyne, a new acetylene-containing lipopeptide, was isolated from a cyanobacterial assemblage that mostly consisted of Lyngbya sp. Its structure was elucidated by spectroscopic analyses and chiral HPLC analyses of hydrolysis products. Kurahyne inhibited the growth of human cancer cells and induced apoptosis in HeLa cells, and it seemed to localize in mitochondria.

Isolation and Total Synthesis of Hoshinolactam, an Antitrypanosomal Lactam from a Marine Cyanobacterium

In the search for new antiprotozoal substances, hoshinolactam, an antitrypanosomal lactam, was isolated from a marine cyanobacterium. The gross structure was elucidated by spectroscopic analyses, and the absolute configuration was determined by the first total synthesis. Hoshinolactam showed potent antitrypanosomal activity with an IC50 value of 3.9 nM without cytotoxicity against human fetal lung fibroblast MRC-5 cells (IC50 > 25 μM).

Isolation and identification of two potential phytotoxic substances from the aquatic fern Marsilea crenata

Organic agriculture emphasized using of biologically originated herbicides and phytotoxic substances are being considered as a replacement to chemical herbicides. Marsilea crenata is an aquatic perennial fern distributed in the South-East Asian countries and is well known for various biological properties. However, to date, there has been no report that addresses the phytotoxicity of Marsilea crenata. Therefore, we explored phytotoxic properties and phytotoxic substances from Marsilea crenata. An aqueous methanol extracts of Marsilea crenata showed inhibition on the seedling growth of cress, lettuce, alfalfa, barnyard grass, Italian ryegrass, and foxtail fescue. Inhibition increased with increasing extract concentration. The extract was purified by several chromatographic steps and two phytotoxic substances were isolated and identified by spectroscopic analysis as loliolide and isololiolide. At the concentration of 30 μM, loliolide and isololiolide inhibited seedling growth of cress and barnyard grass by 41.3 to 51.1%, and 58.15 to 87.5% of control seedlings, respectively. The concentrations required for 50% inhibition of cress and barnyard grass seedlings ranged from 32.1 to 128.5 μM for loliolide, 37.0 to 176.2 μM for isololiolide. These results suggest these compounds may be responsible for phytotoxic effects of Marsilea crenata extract and could be an important part of organic agriculture.

Mebamamides A and B, Cyclic Lipopeptides Isolated from the Green Alga Derbesia marina

Mebamamides A and B, new lipopeptides with four d-amino acid residues and a 3,8-dihydroxy-9-methyldecanoic acid residue, were isolated from the green alga Derbesia marina. Their gross structures were elucidated by spectroscopic and ESI-ITMS analyses. The absolute configurations except for the two leucines were revealed based on chiral-phase HPLC analyses of the acid hydrolysate and a modified Moshers method. A distinction between D-Leu and L-Leu in the sequence was established by the application of a dansyl-Edman method to the partial acid hydrolysate. Mebamamide A did not exhibit any growth inhibitory activity against HeLa and HL60 cells at 10 μM, and mebamamide B did not exhibit any growth inhibitory activity against those cells at 100 μM. Additionally, it was suggested that mebamamide B induced the differentiation of HL60 cells into macrophage-like cells at 100 μM.

Kohamamides A, B, and C, Cyclic Depsipeptides from an Okeania sp. Marine Cyanobacterium

Kohamamides A, B, and C (1-3), new cyclic depsipeptides that belong to the kulolide superfamily, were isolated from an Okeania sp. marine cyanobacterium. Their structures were elucidated by spectroscopic analyses and degradation reactions. Kohamamide B (2) exhibited moderate cytotoxicity against HL60 cells. Although many natural products in the kulolide superfamily have been isolated from cyanobacteria collected in various parts of the world, kohamamides 1-3 are the first members to be isolated from the East Asian marine environment. In addition, unlike other members of this superfamily, kohamamides 1-3 contain a Leu residue adjacent to the Pro residue, rather than another lipophilic amino acid.

Anti-obesity activities of the yoshinone A and the related marine γ-pyrone compounds.

Marine cyanobacteria are known as important creators of novel natural products. From this valuable source, various bioactive compounds have been found and characterized in terms of their pharmacological and toxicological activities.1 In the previous work, we have reported on the isolation and structure determination of potent cytotoxic compounds, lyngbyacyclamide A and B;2 an inhibitor of osteoclastogenesis, biselyngbyaside;3 and a protein kinase inhibitor, bisebromoamide.4 In the recent work, we have reported the new marine γ-pyrones yoshinone A, B1 and B2 from Leptolyngbya sp., and determined their planar structures using NMR spectral analysis.5 Yoshinone A, as the major compound among them, showed inhibitory activity against the adipogenic differentiation of 3T3-L1 cells with an half maximal inhibitory concentration (IC50) value of 420 nm without cytotoxicity (IC50>50 μm). On the other hand, the yoshinone B1 and B2 showed only limited activity against 3T3-L1 cells, with higher concentrations compared with yoshinone A. Further studies of the structure–activity relationship lead us to conclude that the position of a pyrone ring and an olefin in the side chain will be important for the inhibition of adipogenic differentiation. These γ-pyrones have olefins in their side chain at positions 7 and 6 in the cases of yoshinones A and B1/B2, respectively. To express the effects on adipocyte, the olefin should not be conjugated with γ-pyrone moiety, such as yoshinone A (Figure 1). In the previous studies, kalkipyrone6 isolated from cyanobacteria, aureothin,7 and actinopyrones A and B8 isolated from streptomyces fell into the same 7-en γ-pyrones. Then, we confirmed that kalkipyrone and aureothin showed this activity, with IC50 values of 67.5 and 54.2 nm, respectively. On the basis of these data, we are focusing on the 7-en γ-pyrone (unconjugated type) compounds. These pyrones are expected to be candidates for novel lead compounds for the treatment of obesity and related diseases.9 Studies on useful tools that regulate adipocytes will contribute to the prevention and treatment of these diseases. At the present stage of our research, we have evaluated the anti-obesity activities of the 7-en γ-pyrones using in vitro and in vivo experiments. In this study, we report on the interesting properties of these pyrones.

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).