Published Papers - JOMORI Takahiro

Onnamides A and B Suppress Hepatitis B Virus Transcription by Inhibiting Viral Promoter Activity

林 康広

Marine drugs ( MDPI AG )  24 ( 1 ) 21   2026.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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We recently reported that onnamide A, a marine-derived natural compound isolated from the sponge Theonella sp., inhibits the entry process of SARS-CoV-2 infection. However, its antiviral activity against other viruses remains largely unexplored. Here, we investigated the effects of onnamide A and its structurally related analog, onnamide B, on hepatitis B virus (HBV) infection. Using iNTCP cells, a hepatoblastoma-derived cell line permissive to HBV infection, we found that onnamides A and B exhibited cytotoxicity, with CC50 values of 0.53 ± 0.10 μM and 2.37 ± 0.25 μM, respectively. Following HBV infection, the levels of total HBV RNA were significantly reduced by onnamide A (IC50 = 0.06 ± 0.01 μM) and onnamide B (IC50 = 0.23 ± 0.06 μM). Notably, both compounds markedly decreased the levels of HBV pregenomic RNA. Furthermore, significant inhibition was particularly evident when onnamide treatment was initiated after HBV infection. Consistent with these observations, onnamides did not affect HBV binding, entry, or covalently closed circular DNA formation, but they significantly suppressed HBV RNA transcription. In particular, the transcriptional activities driven by the core and X promoters were markedly inhibited by onnamide treatment. Taken together, our findings demonstrate that onnamides possess potent anti-HBV activity and highlight their potential as candidate compounds targeting HBV RNA transcription.

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Demethylmycemycin A, a dibenzoxazepinone from the marine-derived <i>Dactylosporangium</i> sp. OK1079, with prostate cancer suppressive effects via targeting BRK-FAK-STAT3 axis

Elsbaey, M; Tarun, MTI; Alnajjar, R; Jomori, T; Tanaka, J; Oku, N; El Sayed, K; Igarashi, Y

JOURNAL OF ANTIBIOTICS ( Journal of Antibiotics )  79 ( 1 ) 1 - 14   2025.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Integrated biological and chemical investigation of papuan marine organisms for the discovery of potential cytotoxic marine natural products

Hanif, N; Pakan, JS; Lisias, SC; Sael, WB; Santosa, NF; Tyas, TA; Lemuel, MM; Mohamad, K; Sa'diah, S; Dewi, FNA; Oluwabusola, ET; Tsunematsu, Y; Tan, LT; Chasanah, E; Murni, A; de Voogd, NJ; Jomori, T; Kita, M; Jaspars, M; Tanaka, J

NATURAL PRODUCT RESEARCH ( Natural Product Research )    1 - 6   2025.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Onnamides and a Novel Analogue, Onnamide G, as Potent Leishmanicidal Agents.

Jomori T, Higa N, Tyas TA, Matsuura N, Ueda Y, Suetake A, Miyazaki S, Watanabe S, Arizono S, Hayashi Y, Yasumoto K, Ise Y, Wakimoto T, Yasumoto-Hirose M, Tanaka J, Mori-Yasumoto K

Marine biotechnology (New York, N.Y.)   27 ( 5 ) 132   2025.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A Novel Sesterterpenoid, Petrosaspongin and γ-Lactone Sesterterpenoids with Leishmanicidal Activity from Okinawan Marine Invertebrates

Jomori, T; Higa, N; Hokama, S; Tyas, TA; Matsuura, N; Ueda, Y; Kimura, R; Arizono, S; de Voogd, NJ; Hayashi, Y; Yasumoto-Hirose, M; Tanaka, J; Mori-Yasumoto, K

MARINE DRUGS ( Marine Drugs )  23 ( 1 ) 16 - 16   2025.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Leishmaniasis is a major public health problem, especially affecting vulnerable populations in tropical and subtropical regions. The disease is endemic in 90 countries, and with millions of people at risk, it is seen as one of the ten most neglected tropical diseases. Current treatments face challenges such as high toxicity, side effects, cost, and growing drug resistance. There is an urgent need for safer, affordable treatments, especially for cutaneous leishmaniasis (CL), the most common form. Marine invertebrates have long been resources for discovering bioactive compounds such as sesterterpenoids. Using bioassay-guided fractionations against cutaneous-type leishmaniasis promastigotes, we identified a novel furanosesterterpenoid, petrosaspongin from Okinawan marine sponges and a nudibranch, along with eight known sesterterpenoids, hippospongins and manoalides. The elucidated structure of petrosaspongin features a β-substituted furane ring, a tetronic acid, and a conjugated triene. The sesterterpenoids with a γ-butenolide group exhibited leishmanicidal activity against Leishmania major promastigotes, with IC50 values ranging from 0.69 to 53 μM. The structure–activity relationship and molecular docking simulation suggest that γ-lactone is a key functional group for leishmanicidal activity. These findings contribute to the ongoing search for more effective treatments against CL.

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Two isoledene-type sesquiterpenoids from a soft coral<i> Heteroxenia</i> sp.

Kurnianda, V; Hu, HC; Sung, PJ; Hayashi, Y; Mori-Yasumoto, K; Suetake, A; Nakayama, H; Yasumoto-Hirose, M; Tsutsumi, Y; Koja, G; Tsai, YC; Jomori, T; Tanaka, J

TETRAHEDRON LETTERS ( Tetrahedron Letters )  151   155323 - 155323   2024.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Parallel loss of sex in field populations of a brown alga sheds light on the mechanisms underlying the emergence of asexuality

Masakazu Hoshino, Guillaume Cossard, Fabian B. Haas, Emma I. Kane, Kazuhiro Kogame, Takahiro Jomori, Toshiyuki Wakimoto, Susana M. Coelho

Nature Ecology & Evolution ( Cold Spring Harbor Laboratory )  8   1916 - 1932   2024.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Abstract Sexual reproduction is widespread among eukaryotes, but asexual lineages have repeatedly arisen from sexual ancestors across a wide range of taxa. Despite extensive research on the evolution of asexuality from sexual ancestors, the molecular changes underpinning the switch to asexual reproduction remain elusive, particularly in organisms with haploid sexual systems such as bryophytes, and red and brown algae in which males and females are haploid and multicellular. Here, we investigate independent events in which asexuality has emerged from sexual ancestor lineages in species of the brown algalScytosiphon, we examine the proximate and evolutionary mechanisms involved, and test the importance of sexual conflict on gene expression changes following loss of sex. We find that individuals from asexual, female-only (‘Amazon’) populations lose their ability to produce and sex pheromone and, consequently, are unable to attract and fuse with male gametes, whereas they gain the ability to trigger parthenogenic (asexual) development from large, unfertilized eggs. This independent and convergent decline in pheromone production and optimization of asexual traits is accompanied by convergent changes in gene expression, including de-feminization and masculinization of the Amazon gamete transcriptomes. These data are consistent with the idea that decay of female functions, rather than relaxation of sexual antagonism, is the dominant force at play during the emergence of asexuality in haploid sexual systems. Moreover, we identify a locus on an autosomal protein-coding gene that is associated with the switch to asexuality. We propose that the sex chromosome, together with this autosomal locus, may underlie the switch to obligate asexuality in the Amazon populations.

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Onnamide A suppresses the severe acute respiratory syndrome-coronavirus 2 infection without inhibiting 3-chymotrypsin-like cysteine protease

Hayashi, Y; Higa, N; Yoshida, T; Tyas, TA; Mori-Yasumoto, K; Yasumoto-Hirose, M; Tani, H; Tanaka, J; Jomori, T

JOURNAL OF BIOCHEMISTRY ( Journal of Biochemistry )  176 ( 3 ) 197 - 203   2024.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Abstract Given the continuous emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of new inhibitors is necessary to enhance clinical efficacy and increase the options for combination therapy for the coronavirus disease 2019. Because marine organisms have been a resource for the discovery of numerous bioactive molecules, we constructed an extract library of marine invertebrates collected from the Okinawa Islands. In this study, the extracts were used to identify antiviral molecules against SARS-CoV-2. Using a cytopathic effect (CPE) assay in VeroE6/TMPRSS2 cells, an extract from the marine sponge Theonella swinhoei was found to reduce virus-induced CPE. Eventually, onnamide A was identified as an antiviral compound in the extract using column chromatography and NMR analysis. Onnamide A inhibited several SARS-CoV-2 variant-induced CPEs in VeroE6/TMPRSS2 cells as well as virus production in the supernatant of infected cells. Moreover, this compound blocked the entry of SARS-CoV-2 pseudo-virions. Taken together, these results demonstrate that onnamide A suppresses SARS-CoV-2 infection, which may be partially related to entry inhibition, and is expected to be a candidate lead compound for the development of anti-SARS-CoV-2 drugs.

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Okichromanone, a new antiviral chromanone from a marine-derived <i>Microbispora</i>

Elsbaey, M; Jomori, T; Tanaka, J; Oku, N; Igarashi, Y

JOURNAL OF ANTIBIOTICS ( Journal of Antibiotics )  77 ( 6 ) 389 - 392   2024.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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RiPP enzyme heterocomplex structure-guided discovery of a bacterial borosin α-N-methylated peptide natural product

Kathryn K. Crone, Takahiro Jomori, Fredarla S. Miller, Jeffrey Gralnick, Mikael Elias, Michael Freeman.

RSC Chemical Biology ( The Royal Society of Chemistry )  4 ( 10 ) 804 - 816   2023.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Through a combination of in vitro structure–activity assays, crystallography, and in vivo knockout experiments, we have identified and structurally characterized the first bacterial borosin natural product.

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Membrane-Vesicle-Mediated Interbacterial Communication Activates Silent Secondary Metabolite Production

Aya Yoshimura, Rio Saeki, Ryusuke Nakada, Shota Tomimoto, Takahiro Jomori, Keisuke Suganuma, Toshiyuki Wakimoto

Angewandte Chemie-International Edition ( ドイツ化学会 )  62 ( 42 ) e202307304   2023.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Amitorin, a Cytotoxic Diterpenoid from a Sponge Halichondria sp.

Wauke Tsuyoshi, Hanif Novriyandi, Ohlinger Sean, de Voogd Nicole Joy, Kurnianda Viqqi, Jomori Takahiro, Tanaka Junichi

Chemistry Letters ( 公益社団法人 日本化学会 )  51 ( 11 ) 1080 - 1082   2022.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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<p>A new diterpenoid endoperoxide showing cytotoxicity named amitorin (<b>1</b>) was isolated from an extract of a sponge <i>Halichondria</i> sp. Its structure along with relative stereochemistry was elucidated with spectral analysis and calculation studies. The structure and cytotoxicity (IC₅₀ 2.3 µM against NBT-II cells) of the molecule are described herein.</p>

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Insights into phosphatase-activated chemical defense in a marine sponge holobiont

Takahiro Jomori, Kenichi Matsuda, Yoko Egami, Ikuro Abe, Akira Takai, Toshiyuki Wakimoto

RSC CHEMICAL BIOLOGY ( ROYAL SOC CHEMISTRY )  2 ( 6 ) 1600 - 1607   2021.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Marine sponges often contain potent cytotoxic compounds, which in turn evokes the principle question of how marine sponges avoid self-toxicity. In a marine sponge Discodermia calyx, the highly toxic calyculin A is detoxified by the phosphorylation, which is catalyzed by the phosphotransferase CalQ of a producer symbiont, "Candidatus Entotheonella" sp. Here we show the activating mechanism to dephosphorylate the stored phosphocalyculin A protoxin. The phosphatase specific to phosphocalyculin A is CalL, which is also encoded in the calyculin biosynthetic gene cluster. CalL represents a new clade and unprecedently coordinates the heteronuclear metals Cu and Zn. CalL is localized in the periplasmic space of the sponge symbiont, where it is ready for the on-demand production of calyculin A in response to sponge tissue disruption.

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Geographical parthenogenesis in the brown alga Scytosiphon lomentaria (Scytosiphonaceae): Sexuals in warm waters and parthenogens in cold waters

Masakazu Hoshino, Shimpei F. Hiruta, Maria Emilia Croce, Mitsunobu Kamiya, Takahiro Jomori, Toshiyuki Wakimoto, Kazuhiro Kogame

MOLECULAR ECOLOGY ( WILEY )  30 ( 22 ) 5814 - 5830   2021.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Geographical parthenogenesis, a phenomenon where parthenogens and their close sexual relatives inhabit distinct geographical areas, has been considered an interesting topic in evolutionary biology. Reports of geographical parthenogenesis from land and freshwater are numerous, but this occurrence has been rarely reported from the sea. Brown algae are mostly marine and are thought to include numerous obligate parthenogens; still, little is known about the distribution, origin and evolution of parthenogens in this group. Here we report a novel pattern of geographical parthenogenesis in the isogamous brown alga Scytosiphon lomentaria. Sex ratio investigation demonstrated that, in Japan, sexual populations grew in the coast along warm ocean currents, whereas female-dominant parthenogenetic populations grew mainly in the coast along a cold ocean current. In the two localities where sexual and parthenogenetic populations were parapatric, parthenogens grew in more wave-exposed areas than sexuals. Population genetic and phylogenetic analyses, including those based on genome-wide single nucleotide polymorphism data, indicated that parthenogens have initially evolved at least twice and subsequent hybridizations between the parthenogens and sexuals have generated multiple new parthenogenetic lineages. The origin of the initial parthenogens is not clear, except that it would not be interspecies hybridization. Interestingly, we found that the production of sex pheromones, which attract male gametes, has been independently lost in the initial two parthenogenetic lineages. This parallel loss of the sexual trait may represent the direct origin of parthenogens, or the regressive evolution of a useless trait under asexuality.

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Mycobacterium smegmatis alters the production of secondary metabolites by marine-derived Aspergillus niger

Takahiro Jomori, Yasumasa Hara, Miho Sasaoka, Kazuo Harada, Andi Setiawan, Kazumasa Hirata, Atsushi Kimishima, Masayoshi Arai

JOURNAL OF NATURAL MEDICINES ( SPRINGER JAPAN KK )  74 ( 1 ) 76 - 82   2020.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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It is generally accepted that fungi have a number of dormant gene clusters for the synthesis of secondary metabolites, and the activation of these gene clusters can expand the diversity of secondary metabolites in culture. Recent studies have revealed that the mycolic acid-containing bacterium Tsukamurella pulmonis activates dormant gene clusters in the bacterial genus Streptomyces. However, it is not clear whether the mycolic acid-containing bacteria activate dormant gene clusters of fungi. We performed co-culture experiments using marine-derived Aspergillus niger with Mycobacterium smegmatis, a mycolic acid-containing bacteria. The co-cultivation resulted in the production of a pigment by A. niger and increased cytotoxic activity of the extract against human prostate cancer DU145 cells. An analysis of secondary metabolites in the extract of the co-culture broth revealed that the increase in cytotoxic activity was caused by the production of malformin C (1), and that TMC-256A1 (2), desmethylkotanin (3), and aurasperone C (4) were selectively produced under co-culture conditions. In addition, further study suggested that direct interaction between the two microorganisms was necessary for the production of the pigment and the cytotoxic compound malformin C (1) from A. niger. Given the biological activities of malformin C, including cytotoxic activity, our approach for increasing the production of bioactive secondary metabolites has important practical applications and may facilitate structural analyses of novel bioactive compounds.

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Scrobiculosides A and B from the deep-sea sponge Pachastrella scrobiculosa

Takahiro Jomori, Shuji Shiroyama, Yuji Ise, Hisanori Kohtsuka, Kenichi Matsuda, Takefumi Kuranaga, Toshiyuki Wakimoto

JOURNAL OF NATURAL MEDICINES ( SPRINGER JAPAN KK )  73 ( 4 ) 814 - 819   2019.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Two new steroidal saponins, scrobiculosides A and B, were isolated from the deep-sea sponge Pachastrella scrobiculosa, collected at a depth of 200 m off Miura Peninsula, Japan. The aglycones of scrobiculosides A and B feature a vinylic cyclopropane and a ∆24,25 exomethylene on the side chains, respectively. Both saponins have a common sugar moiety composed of β-D-galactopyranosyl-(1 → 2)-6-acetyl-β-D-glucopyranoside, with the exception of an acetyl group on C6″ in scrobiculoside A. Scrobiculoside A exhibited cytotoxicity against HL-60 and P388 cells, with IC50 values of 52 and 61 μM, respectively.

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Cytotoxicity of New Diterpene Alkaloids, Ceylonamides G-I, Isolated From Indonesian Marine Sponge of Spongia sp.

Takahiro Jomori, Andi Setiawan, Miho Sasaoka, Masayoshi Arai

NATURAL PRODUCT COMMUNICATIONS ( SAGE PUBLICATIONS INC )  14 ( 6 )   2019.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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In the course of the search for cancer cell growth inhibitors, 3 new diterpene alkaloids, designated ceylonamides G-I (1-3), together with ceylonamide F (4) were isolated from an Indonesian marine sponge of Spongia sp. The chemical structures of compounds 1-3 were determined using spectroscopic analysis and compared with those of compound 4. Among the isolated compounds, 1 and 4 inhibited the growth of human prostate cancer DU145 cells in a two-dimensional monolayer culture, with an IC50 of 6.9 and 18.8 mu M, respectively. Furthermore, these compounds are also effective on spheroid of three-dimensional cell culture model, which was prepared from DU145 cells. Based on the morphological changes in the spheroids, the minimum effective concentrations of compounds 1 and 4 were 10 and 25 mu M, respectively.

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Peridinin, a carotenoid, inhibits proliferation and survival of HTLV-1-infected T-cell lines.

Chie Ishikawa, Takahiro Jomori, Junichi Tanaka, Masachika Senba, Naoki Mori

International journal of oncology ( International Journal of Oncology )  49 ( 4 ) 1713 - 21   2016.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Human T-cell leukemia virus type 1 (HTLV-1) causes either adult T-cell leukemia (ATL) or chronic inflammatory disorders such as HTLV-1-associated myelopathy/tropical spastic paraparesis. These diseases are not curable as yet; therefore new agents for treatment and prevention are needed. Carotenoids are natural plant compounds with anti-carcinogenic activities. Peridinin is one of the most abundant carotenoids found in nature. Based on a series of past experiments, here we investigated the effects of peridinin extracted from Okinawan coral Isis hippuris on the proliferation and survival of HTLV-1-infected T-cell lines. The results of water-soluble tetrazolium-8 assay indicated that peridinin dose-dependently inhibits cell proliferation and viability of HTLV-1-infected T-cell lines. Flow cytometry showed that low concentration of peridinin induced cell cycle arrest at G1 phase, while higher concentration induced apoptosis. Peridinin caused cleavage of caspase-3, -8 and -9. Peridinin significantly reduced the expression of G1 cell cycle regulators, including cyclin D1, cyclin D2, CDK4, CDK6 and c-Myc, and anti-apoptotic proteins, including survivin, XIAP and Bcl-2, in a dose-dependent manner. Peridinin suppressed DNA binding of NF-κB. Peridinin inhibited phosphorylation of IκBα, RelA, Akt and p70 S6 kinase, and reduced protein expression level of 3-phosphoinositide-dependent protein kinase 1. Thus, peridinin exerts its anti-proliferative and pro-apoptotic effects by suppressing NF-κB and Akt signaling in HTLV-1-infected T cells. Peridinin also reduced tumor growth in mice harboring ATL xenograft tumors. The results suggested that peridinin is a potentially suitable therapeutic agent against HTLV-1-associated diseases.

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A New Isocyanosesquiterpene from the Nudibranch Phyllidiella pustulosa

Takahiro Jomori, Takahiro Shibutani, Peni Ahmadi, Toshimasa Suzuka, Junichi Tanaka

NATURAL PRODUCT COMMUNICATIONS ( NATURAL PRODUCTS INC )  10 ( 11 ) 1913 - 1914   2015.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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In the course of our study on the chemical and genetic diversity of the nudibranch Phylidiella pustulosa, we identified a series of isocyanosesquiterpenes. In addition to known sesquitetpenes, we isolated a new molecule 1, the structure of which was elucidated by analyzing NMR. and other spectral data. We report the structure and cytotoxicity of compound 1 herein.