Details of a Researcher - Suenaga, Kiyotake

Papers - Suenaga, Kiyotake

Division display 1 - 20 of about 262 ／ All the affair displays >>

Isolation and Total Synthesis of Ukabamide, an Antitrypanosomal Lipopeptide from a Marine Moorena sp. Cyanobacterium

Hagihara M., Kurisawa N., Iwasaki A., Taguchi R., Jeelani G., Nozaki T., Suenaga K.

Organic Letters 2025

ISSN 15237060

Human African trypanosomiasis (HAT) is one of the most lethal of the neglected tropical diseases. While the discovery of a novel antitrypanosomal drug is highly desired, the creation of a superior lead compound is challenging. Herein we report ukabamide (1), which was isolated from a marine Moorena sp. cyanobacterium, as a selective and potent antitrypanosomal lipopeptide (IC50 = 34 ± 18 nM against Trypanosoma brucei rhodesiense). Its structure was elucidated by spectroscopic analyses and degradation reactions and confirmed by total synthesis. In addition, we prepared two modified analogs and revealed the importance of the fatty acid chain length for biological activity. These findings may provide design guidelines for an antitrypanosomal drug.

Access to Document (DOI)

Hedopeptolide, a NO Production Inhibitor from the Marine Cyanobacterium Okeania sp.

Tojo S., Natsume N., Niino T., Iwasaki A., Suenaga K., Ohno O., Teruya T.

Journal of Natural Products 2025

ISSN 01633864

Access to Document (DOI)

Sealgamide: An Antitrypanosomal Lipopeptide Isolated from a Marine Okeania sp. Cyanobacterium

Wakai K., Kurisawa N., Umeda K., Jeelani G., Agusta A.L., Nozaki T., Suenaga K.

Journal of Natural Products 2025

ISSN 01633864

Sealgamide (1), a new antitrypanosomal lipopeptide, was isolated from a marine Okeania sp. cyanobacterium. Elucidation of its structure was challenging due to signal overlap caused by conspicuous rotamers but was ultimately achieved through partial hydrolysis and subsequent spectroscopic analyses. Sealgamide (1) exhibited moderate antitrypanosomal activity against Trypanosoma brucei rhodesiense (IC50 2.9 μM) while showing no antimalarial activity (IC50 > 25 μM) or cytotoxicity (IC50 > 30 μM). Furthermore, we discovered that an artificial C-terminal methyl ester analogue (2) exhibited notably enhanced antiparasitic activity.

Access to Document (DOI)

Toxicity of the marine glycosidic macrolides, polycavernoside E and akunolides, from Okinawan cyanobacterium Okeania sp. in mice

Yotsu-Yamashita M., Umeda K., Iwasaki A., Suenaga K.

Toxicon 250 2024.11

ISSN 00410101

The toxicity of polycavernoside E and its structurally related macrolides, akunolides A, B, and C, was evaluated in mice. These compounds were recently isolated from the marine cyanobacterium Okeania sp. collected in Okinawa, Japan. The minimal toxicity of polycavernoside E was estimated as 0.81 mg/kg by intraperitoneal injection, whereas those of akunolides A–C were >13 mg/kg. Owing to the considerable toxicity of polycavernoside E, the occurrence of this cyanobacterium should be considered in seaweed production environments.

Access to Document (DOI)

The Bioorganic Study of Iezoside: A Novel SERCA Inhibitor from the Marine Cyanobacterium

Kurisawa N., Iwasaki A., Suenaga K.

Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry 82 ( 11 ) 1107 - 1116 2024.11

ISSN 00379980

In this era of advanced technologies, is there still wisdom to be gleaned from nature? The answer is an unequivocal “Yes”. Discovering new natural products from nature, determining their structures, and revealing their biological activities ‐ this classical natural product chemistry is still a catalyst for innovation in a wide range of fields, including the expansion of chemical space, elucidation of life phenomena, and drug discovery. In this account, we describe a comprehensive bioorganic study of iezoside (1a), the novel marine natural product we recently discovered, including its discovery, synthesis, mode of action, and structure‐activity relationships.

Access to Document (DOI)

Allelopathic Activity of Leaf Wastes of Liriodendron tulipifera for Sustainable Management

Kato-Noguchi H., Hayashi K., Iwasaki A., Suenaga K.

Applied Sciences (Switzerland) 14 ( 18 ) 2024.09

Logging operations of Liriodendron tulipifera L., as timber trees, and fallen leaves in autumn from ornamental trees produce a large amount of leaf waste. In this study, the allelopathy of L. tulipifera fresh and fallen leaves was investigated for the development of potential applications of leaf waste. The extracts of fresh and fallen leaves of L. tulipifera showed growth inhibitory activity against weed species, Vulpia myuros (L.) C.C.Gmel., Echinochloa crus-galli (L.) P.Beauv., and Lolium multiflorum Lam., under laboratory conditions. The powder of L. tulipifera fresh and fallen leaves also inhibited the germination of E. crus-galli under greenhouse conditions. A potent allelochemical was isolated from fresh and fallen leaf extracts through a bioassay-guided separation process, and was identified as lipiferolide. Lipiferolide inhibited the growth of L. multiflorum and Lepidum sativum in a concentration-dependent manner. This investigation suggests that the leaf waste of L. tulipifera from logging operations and fallen leaves is potentially useful for the purpose of weed control, such as through the use of soil additive materials from leaves or the creation of foliar spray from leaf extracts. The development of weed control materials using L. tulipifera leaf waste may be a means with which to minimize waste, reducing environmental impacts and economic concerns.

Access to Document (DOI)

Wajeepeptin, a Cytotoxic and Antitrypanosomal Cyclic Depsipeptide from a Marine Moorena sp. Cyanobacterium

Kurisawa N., Jeelani G., Nozaki T., Agusta A.L., Suenaga K., Iwasaki A.

Journal of Natural Products 87 ( 7 ) 1838 - 1843 2024.07

ISSN 01633864

Access to Document (DOI)

Structure–activity relationship studies on iezoside, a highly potent Ca<sup>2+</sup> ATPase inhibitor

Kurisawa N., Teranuma K., Noto A., Iwasaki A., Kabashima Y., Nakajima R., Toyoshima C., Suenaga K.

Bulletin of the Chemical Society of Japan 97 ( 7 ) 2024.07

ISSN 00092673

Iezoside (1a) is a novel, potent sarco-/endoplasmic reticulum Ca2+ ATPase (SERCA) inhibitor from marine cyanobacterium. This paper describes the synthesis of comprehensive iezoside (1a) analogs containing C-18/19 diastereomers, simplified analogs without the peptide unit, and aglycones. Evaluations of the antiproliferative activities against cancer cells and SERCA inhibitory activities of the synthesized analogs revealed how the absolute configurations at C-18/19, peptide, and the sugar unit contribute to each bioactivity.

Access to Document (DOI)

Allelopathy and Allelochemicals in Chamaecyparis obtusa Leaves for the Development of Sustainable Agriculture

Kato-Noguchi H., Mori K., Iwasaki A., Suenaga K.

Agronomy 14 ( 7 ) 2024.07

Chamaecyparis obtusa (Siebold et Zucc.) Endl. is cultivated in the temperate region of East Asia for its high-quality and profitable timber. The timber-processing industry produces a large amount of waste, such as tree bark, branches, and leaves, and finding ways to minimize such waste is economically and environmentally efficient. In the present study, the allelopathic activity and allelochemicals of the C. obtusa leaves were investigated to develop potential application methods. C. obtusa leaves were phytotoxic and associated leaf extracts significantly suppressed the growth of the weeds; Echinochloa crus-galli, Phleum pratense and Lolium multiflorum under laboratory conditions. The leaf powder applied onto the soil surface also suppressed the germination of E. crus-galli and P. pratense under greenhouse conditions. Hinokiic acid and (+)-dihydrosesamin were isolated from the leaves and structurally identified. Both compounds suppressed the growth of cress and P. pratense in a concentration dependent manner. When the leaves of C. obtua were applied as a soil additive, hinokiic acid and (+)-dihydrosesamin in the leaves potentially cause the growth inhibitory activity by leaching into the soil. These experiments showed that the leaves and the leaf extracts of C. obtusa are phytotoxic. These experiments also demonstrated that the leaves and the leaf extracts of C. obtusa have growth inhibitory potential against several plant species, and the leaves produce allelochemicals. Therefore, the leaves and leaf extracts of C. obtusa may be useful for weed suppression purposes. The leaf biomass of C. obtusa is frequently large and the timber processing industry produces significant leaf waste. The development of weed control products using waste leaves may be a solution to minimize the timber processing waste to reduce environmental impact and provide economic value. However, leaf material should be evaluated for weed suppression and herbicidal activity as a soil additive and also possible as a foliar spray under field conditions.

Access to Document (DOI)

Kagimminols A and B, Cembrene-Type Diterpenes from an Okeania sp. Marine Cyanobacterium

Ebihara A., Taguchi R., Jeelani G., Nozaki T., Suenaga K., Iwasaki A.

Journal of Natural Products (Journal of Natural Products) 87 ( 4 ) 1116 - 1123 2024.04

ISSN 01633864

Kagimminols A (1) and B (2), new cembrene-type diterpenoids, were isolated from an Okeania sp. marine cyanobacterium. By combining DP4 analysis with an efficient NMR chemical shift calculation protocol, we clarified the relative configurations of 1 and 2 without consuming precious natural products. We determined the absolute configurations by a comparison of theoretical electronic circular dichroism (ECD) spectra with experimental spectra, and the absolute configuration of 1 was verified experimentally. Finally, we found that 1 and 2 showed selective growth-inhibitory activity against the causative agent of human African trypanosomiasis. This study exemplifies that computational chemistry is an efficient tool for clarifying the configurations of natural products possessing tautomers in equilibrium.

Access to Document (DOI)

Isolation and structure determination of a new analog of polycavernosides from marine Okeania sp. cyanobacterium

Umeda K., Kurisawa N., Jeelani G., Nozaki T., Suenaga K., Iwasaki A.

Beilstein Journal of Organic Chemistry (Beilstein Journal of Organic Chemistry) 20 645 - 652 2024

Polycavernoside E (1), a new polycavernoside analog, was isolated from a marine Okeania sp. cyanobacterium. The relative configuration was elucidated primarily by analyzing the two dimensional nuclear magnetism resonance (2D NMR) data. The absolute configuration was clarified by comparing the electronic circular dichroism (ECD) data of 1 with those of known analogs. Polycavernoside E (1) exhibited moderate antitrypanosomal activity against Trypanosoma brucei rhodesiense. Furthermore, the isolation of polycavernoside E (1) from marine cyanobacteria provides additional evidence that marine cyanobacteria, and not red algae, are responsible for the biosynthesis of polycavernosides.

Access to Document (DOI)

Allelopathic potential of Oldenlandia corymbosa and identification of its allelopathic substances

Kyaw E.H., Hossen K., Iwasaki A., Suenaga K., Kato-Noguchi H.

Plant Biosystems (Plant Biosystems) 158 ( 3 ) 394 - 403 2024

ISSN 11263504

The use of allelopathy developed as an alternative practice for weed management in agriculture. Oldenlandia corymbosa is an annual herb and notable for being applied in folk medicine. Its diverse range of pharmacological properties and several bioactive substances have been well reported. Nevertheless, the allelopathic potential of O. corymbosa has not yet been documented. Hence, we aim to explore the allelopathy of O. corymbosa for weed control purposes. The extracts of O. corymbosa were tested to determine their effects on the seedling growth of six tested species. Significant reductions in the growth of seedling were exhibited as the plant extract concentrations increased. The plant extracts of O. corymbosa were separated in several chromatography steps; two active substances isolated and characterized as hedyotiscone A and B. Hedyotiscone A and B significantly restricted the growth of cress seedling at concentrations higher than 0.3 mM. The I50 values of hedyotiscone A and B for the cress seedlings ranged from 0.023 to 0.131 mM and 0.167 to 0.810 mM, respectively. The inhibitory activity against cress seedlings indicates that hedyotiscone A and B contribute to the allelopathic effects and may be responsible for the allelopathic potential of O. corymbosa.

Access to Document (DOI)

Isolation and Structure Determination of Akunolides, Macrolide Glycosides from a Marine Okeania sp. Cyanobacterium

Umeda K., Iwasaki A., Taguchi R., Kurisawa N., Jeelani G., Nozaki T., Suenaga K.

Journal of Natural Products (Journal of Natural Products) 86 ( 11 ) 2529 - 2538 2023.11

ISSN 01633864

Akunolides A (1), B (2), C (3), and D (4), new macrolide glycosides, were isolated from a marine Okeania sp. cyanobacterium. Their structures were elucidated by spectroscopic analyses and derivatization reactions. Akunolides A-D (1-4) are classified as 16-membered macrolide glycosides, which are relatively rare structures for marine cyanobacterium-derived natural products. Akunolides A-D (1-4) showed moderate antitrypanosomal activities against Trypanosoma brucei rhodesiense, with IC50 values ranging from 11 to 14 μM. Furthermore, akunolides A (1) and C (3) exhibited no cytotoxicity against normal human WI-38 cells even at a concentration of 150 μM.

Access to Document (DOI)

Fumagillin inhibits growth of the enteric protozoan parasite Entamoeba histolytica by covalently binding to and selectively inhibiting methionine aminopeptidase 2

Watanabe N., Saito-Nakano Y., Kurisawa N., Otomo K., Suenaga K., Nakano K., Nozaki T.

Antimicrobial Agents and Chemotherapy (Antimicrobial Agents and Chemotherapy) 67 ( 11 ) 2023.11

ISSN 00664804

Amebiasis is an important cause of morbidity and mortality worldwide, and caused by infection with the protozoan parasite Entamoeba histolytica. Metronidazole is currently the first-line drug despite adverse effects and concerns on the emergence of drug resistance. Fumagillin, a fungal metabolite from Aspergillus fumigatus, and its structurally related natural and synthetic compounds have been previously explored as potential anti-angiogenesis inhibitors for cancers, anti-microbial, and anti-obese compounds. Although fumagillin was used for human amebiasis in clinical trials in 1950s, the mode of action of fumagillin remains elusive until now. In this report, we showed that fumagillin covalently binds to methionine aminopeptidase 2 (MetAP2) and non-covalently but abundantly binds to patatin family phospholipase A (PLA). Susceptibility against fumagillin of the amebic strains in which expression of E. histolytica MetAP2 (EhMetAP2) gene was silenced increased compared to control strain. Conversely, overexpression of EhMetAP2 mutants that harbors amino acid substitutions responsible for resistance to ovalicin, a fumagillin analog, in human MetAP2, also resulted in decrease in fumagillin susceptibility. In contrast, neither gene silencing nor overexpression of E. histolytica PLA (EhPLA) affected fumagillin susceptibility. These data suggest that EhPLA is not essential and not the target of fumagillin for its amebicidal activity. Taken together, our data have demonstrated that EhMetAP2 is the primary target for amebicidal activity of fumagillin, and EhMetAP2 represents a rational explorable target for the development of alternative therapeutic agents against amebiasis.

Access to Document (DOI)

Total synthesis of acetylene-containing lipopeptides odookeanynes A and B

Lo Y.H., Umeda K., Kurisawa N., Jeelani G., Nozaki T., Suenaga K.

Tetrahedron Letters (Tetrahedron Letters) 130 2023.10

ISSN 00404039

Access to Document (DOI)

Total Synthesis of Ikoamide, a Highly N-Methylated Antimalarial Lipopeptide

Lo Y.H., Iwasaki A., Suenaga K.

Journal of Organic Chemistry (Journal of Organic Chemistry) 88 ( 15 ) 10565 - 10573 2023.08

ISSN 00223263

Ikoamide (1) is a highly N-methylated antimalarial lipopeptide that was isolated from a marine cyanobacterium, an Okeania sp. in 2018, which shows strong antimalarial activity without cytotoxicity against human cancer cell lines. To establish a synthetic method for obtaining enough ikoamide for its biological evaluations, we have established a total synthesis of ikoamide. The synthetic method presented here lays the foundation for the development of novel ikoamide analogues, which may lead to a discovery of pharmaceutically unique antimalarial drug leads.

Access to Document (DOI)

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

Ozaki K., Asato Y., Natsume N., Tojo S., Sumimoto S., Iwasaki A., Suenaga K., Teruya T.

Journal of Natural Products (Journal of Natural Products) 86 ( 6 ) 1564 - 1570 2023.06

ISSN 01633864

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.

Access to Document (DOI)

Unique Initiation and Termination Mechanisms Involved in the Biosynthesis of a Hybrid Polyketide-Nonribosomal Peptide Lyngbyapeptin B Produced by the Marine Cyanobacterium Moorena bouillonii

Kudo F., Chikuma T., Nambu M., Chisuga T., Sumimoto S., Iwasaki A., Suenaga K., Miyanaga A., Eguchi T.

ACS Chemical Biology (ACS Chemical Biology) 18 ( 4 ) 875 - 883 2023.04

ISSN 15548929

Lyngbyapeptin B is a hybrid polyketide-nonribosomal peptide isolated from particular marine cyanobacteria. In this report, we carried out genome sequence analysis of a producer cyanobacterium Moorena bouillonii to understand the biosynthetic mechanisms that generate the unique structural features of lyngbyapeptin B, including the (E)-3-methoxy-2-butenoyl starter unit and the C-terminal thiazole moiety. We identified a putative lyngbyapeptin B biosynthetic (lynB) gene cluster comprising nine open reading frames that include two polyketide synthases (PKSs: LynB1 and LynB2), four nonribosomal peptide synthetases (NRPSs: LynB3, LynB4, LynB5, and LynB6), a putative nonheme diiron oxygenase (LynB7), a type II thioesterase (LynB8), and a hypothetical protein (LynB9). In vitro enzymatic analysis of LynB2 with methyltransferase (MT) and acyl carrier protein (ACP) domains revealed that the LynB2 MT domain (LynB2-MT) catalyzes O-methylation of the acetoacetyl-LynB2 ACP domain (LynB2-ACP) to yield (E)-3-methoxy-2-butenoyl-LynB2-ACP. In addition, in vitro enzymatic analysis of LynB7 revealed that LynB7 catalyzes the oxidative decarboxylation of (4R)-2-methyl-2-thiazoline-4-carboxylic acid to yield 2-methylthiazole in the presence of Fe2+ and molecular oxygen. This result indicates that LynB7 is responsible for the last post-NRPS modification to give the C-terminal thiazole moiety in lyngbyapeptin B biosynthesis. Overall, we identified and characterized a new marine cyanobacterial hybrid PKS-NRPS biosynthetic gene cluster for lyngbyapeptin B production, revealing two unique enzymatic logics.

Access to Document (DOI)

Isolation of Hennaminal and Isolation and Total Synthesis of Hennamide, Pyrrolinone Compounds from the Marine Cyanobacterium Rivularia sp.

Takahashi H., Iwasaki A., Ebihara A., Taguchi R., Jeelani G., Nozaki T., Suenaga K.

Organic Letters (Organic Letters) 25 ( 14 ) 2400 - 2404 2023.04

ISSN 15237060

Two new natural products were isolated from the marine cyanobacterium Rivularia sp. collected in Japan. Hennaminal possesses a very rare functional group, β,β-diamino unsaturated ketone, which has only been found in bohemamine-type natural products so far. Hennamide possesses a reactive N-acyl pyrrolinone moiety, which induces self-dimerization. The isolation and structure determination supported by computational chemistry and total synthesis, as well as the antitrypanosomal activities of hennaminal and hennamide are described.

Access to Document (DOI)

Allelopathic Potential of Marsdenia tenacissima (Roxb.) Moon against Four Test Plants and the Biological Activity of Its Allelopathic Novel Compound, 8-Dehydroxy-11β-O-Acetyl-12β-O-Tigloyl-17β-Marsdenin

Moh S.M., Kurisawa N., Suenaga K., Kato-Noguchi H.

Plants (Plants) 12 ( 8 ) 2023.04

Plant parts and extracts that are rich in bioactive substances with allelopathic potential can be explored as a possible alternative to herbicides for natural weed control in sustainable agriculture. In the present study, we investigated the allelopathic potential of Marsdenia tenacissima leaves and its active substances. Aqueous methanol extracts of M. tenacissima showed significant inhibitory activities against the growth of lettuce (Lactuca sativa L.), alfalfa (Medicago sativa L.), timothy (Phleum pratense L.), and barnyard grass (Echinochloa crusgalli (L.) Beauv.). The extracts were purified through various chromatography steps, and one active substance was isolated and determined by spectral data to be a novel compound, assigned as steroidal glycoside 3 (8-dehydroxy-11β-O-acetyl-12β-O-tigloyl-17β-marsdenin). Steroidal glycoside 3 significantly inhibited the seedling growth of cress at a concentration of 0.03 mM. The concentrations needed for 50% growth inhibition of the cress shoots and roots were 0.25 and 0.03 mM, respectively. These results suggest that steroidal glycoside 3 may be responsible for the allelopathy of M. tenacissima leaves.

Access to Document (DOI)

　 Previous page - Next page 　