New benzoyl sesquiterpenoid, aoganolide, produced by Talaromyces sp. KTF-0021 strain (laeA-introduced mutant of FKI-5759 strain).

To discover novel natural compounds by awakening unexplored or silent BGCs in fungi, our research group has explored the cultured broths of the laeA-introduced mutant fungal strains. In this study, we report the isolation of a new benzoyl sesquiterpenoid, aoganolide (4), as well as three known compounds, decarboxyaltenusin (1), altenusin (2), and penipyranicin B (3), from the cultured broth of Talaromyces sp. KTF-0021, which was a laeA-introduced mutant of FKI-5759 strain.

Design and synthesis of novel triazine derivatives as antimalarial agents.

In a previous study, we reported that nilotinib, a BCR-ABL tyrosine kinase inhibitor, possesses moderate antimalarial activity against PfK1 and PfFCR3. As a part of our efforts to develop novel antimalarial agents, a series of novel triazine analogs was identified as potent antimalarial agents via structure modification of nilotinib. Compound 15a showed strong antimalarial activities against PfK1 and PfFCR3 with IC values of 0.

New antimalarial iromycin analogs produced by Streptomyces sp. RBL-0292.

Two new antimalarial compounds, named prenylpyridones A (1) and B (2), were discovered from the actinomycete cultured material of Streptomyces sp. RBL-0292 isolated from the soil on Hamahiga Island in Okinawa prefecture. The structures of 1 and 2 were elucidated as new iromycin analogs having α-pyridone ring by MS and NMR analyses.

Akedanones A-C, and Antiplasmodial 2,3-Dihydronaphthoquinones Produced by sp. K20-0187.

Three new antiplasmodial compounds, named akedanones A (), B (), and C (), were discovered from the cultured material of sp. K20-0187 isolated from a soil sample collected at Takeda, Kofu, Yamanashi prefecture in Japan. The structures of compounds - were elucidated as new 2,3-dihydronaphthoquinones having prenyl and reverse prenyl groups by mass spectrometry and nuclear magnetic resonance analyses.

Virgaricins C and D, new pramanicin analogs produced by Apiospora sp. FKI-8058.

Two new pramanicin analogs, named virgaricins C (1) and D (2), were discovered by physicochemical screening from a static cultured material of Apiospora sp. FKI-8058. Their structures were elucidated by MS and NMR analyses and chemical derivatization.

New antimalarial fusarochromanone analogs produced by the fungal strain Fusarium sp. FKI-9521.

Two new antimalarial compounds, named deacetyl fusarochromene (1) and 4'-O-acetyl fusarochromanone (2), were discovered from the static fungal cultured material of Fusarium sp. FKI-9521 isolated from feces of a stick insect (Ramulus mikado) together with three known compounds fusarochromanone (3), 3'-N-acetyl fusarochromanone (4), and 5 (fusarochromene or banchromene). The structures of 1 and 2 were elucidated as new analogs of 3 by MS and NMR analyses.

Assessment of environmental surface contamination with SARS-CoV-2 in concert halls and banquet rooms in Japan.

Background: Although crowds are considered to be a risk factor for SARS-CoV-2 transmission, little is known about the changes in environmental surface contamination with the virus when a large number of people attend an event. In this study, we evaluated the changes in environmental surface contamination with SARS-CoV-2.

Methods: Environmental samples were collected from concert halls and banquet rooms before and after events in February to April 2022 when the 7-day moving average of new COVID-19 cases in Tokyo was reported to be 5000-18000 cases per day.

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

Two new antiplasmodial peptides, named koshidacins A () and B (), were discovered from the culture broth of the Okinawan fungus FKR-0564. Their structures, including absolute configurations, were elucidated by a combination of spectroscopic methods and chemical derivatization. Both compounds showed moderate antiplasmodial activity against strains, with IC values ranging from 17.

Semisynthesis of Antitrypanosomal p-Quinone Analog Possesing the Komaroviquinone Pharmacophore.

A p-quinone analog having the komaroviquinone pharmacophore fused with a more conformationally flexible cycloheptane ring, was semisynthesized from natural demethlsalvicanol isolated from Perovskia abrotanoides via four steps in 26% overall yield. The IC for the antitrypanosomal activity of the analog was 0.55 µM.

Shikinefragalides A-D, new tricyclic macrolides produced by Stachybotryaceae sp. FKI-9632.

Four new tricyclic macrolides, named shikinefragalides A (1), B (2), C (3) and D (4), were isolated by physicochemical (PC) screening from a static culture material of Stachybotryaceae sp. FKI-9632. Their structures were elucidated as new analogs of colletofragarones by MS and NMR analyses.

Discoveries and Syntheses of Highly Potent Antimalarial Troponoids.

Novel derivatives of puberulic acid were synthesized and their antimalarial properties were evaluated in vitro against the Plasmodium falciparum K1 parasite strain, cytotoxicity against a human diploid embryonic cell line MRC-5, and in vivo efficacy using a Plasmodium berghei-infected mouse model. From previous information that three hydroxy groups on the tropone framework were essential for antimalarial activity, we converted the carboxylic acid moiety into the corresponding esters, amides, and ketones. These derivatives showed antimalarial activity against chloroquine-resistant Plasmodium in vitro equivalent to puberulic acid.

A Concise Total Synthesis of Dehydroantofine and Its Antimalarial Activity against Chloroquine-Resistant Plasmodium falciparum.

The total synthesis of dehydroantofine was achieved by employing a novel, regioselective, azahetero Diels-Alder reaction of easily accessible 3,5-dichloro-2H-1,4-oxazin-2-one with 14 a as a key step. Furthermore, it is demonstrated that dehydroantofine is a promising candidate as a new antimalarial agent in a biological assay with chloroquine-resistant Plasmodium falciparum.

Diatretol, an α, α'-dioxo-diketopiperazine, is a potent in vitro and in vivo antimalarial.

A fungal metabolite, diatretol, has shown to be a promising antimalarial agent. Diatretol displayed potent in vitro antiparasitic activity against the Plasmodium falciparum K1 strain, with an IC value of 378 ng ml, as well as in vivo efficacy in a Plasmodium berghei-infected mice model, with ca. 50% inhibition at 30 mg/kg (p.

Hatsusamides A and B: Two New Metabolites Produced by the Deep-Sea-Derived Fungal Strain FKJ-0213.

Two new nitrogen-containing metabolites, designated hatsusamide A () and B (), were isolated from a culture broth of FKJ-0213 together with the known compounds tanzawaic acid B () and trichodermamide C () by physicochemical (PC) screening. The structures of and were determined as a tanzawaic acid B-trichodermamide C hybrid structure and a new analog of aspergillazines, respectively. The absolute configuration of was determined by comparing the values of tanzawaic acid B and trichodermamide C in the literatures, such as H-nuclear magnetic resonance (H-NMR) data and optical rotation, after hydrolysis of .

Discovery of 3-Cinnamamido-N-Substituted Benzamides as Potential Antimalarial Agents.

Background: Malaria is one of the most devastating parasitic diseases, yet the discovery of antimalarial agents remains profoundly challenging. Very few new antimalarials have been developed in the past 50 years, while the emergence of drug-resistance continues to appear.

Objective: This study focuses on the discovery, design, synthesis, and antimalarial evaluation of 3- cinnamamido-N-substituted benzamides.

Rapid and Systematic Exploration of Chemical Space Relevant to Artemisinins: Anti-malarial Activities of Skeletally Diversified Tetracyclic Peroxides and 6-Aza-artemisinins.

To achieve both structural changes and rapid synthesis of the tetracyclic scaffold relevant to artemisinins, we explored two kinds of synthetic approaches that generate both skeletally diversified tetracyclic peroxides and 6-aza-artemisinins. The anti-malarial activities of the tetracyclic peroxides with distinct skeletal arrays, however, were moderate and far inferior to artemisinins. Given the privileged scaffold of artemisinins, we next envisioned element implantation at the C6 position with a nitrogen without the trimmings of substituents and functional groups.

Clonocoprogens A, B and C, new antimalarial coprogens from the Okinawan fungus Clonostachys compactiuscula FKR-0021.

Three new antimalarial compounds, clonocoprogens A, B, and C, were isolated from the static culture of an Okinawan fungus, Clonostachys compactiuscula FKR-0021. These compounds were new analogs of N-palmitoylcoprogen, reported as a siderophore. They showed moderate antimalarial activity against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains, with IC values ranging from 1.

Kozupeptins, Antimalarial Agents Produced by Paracamarosporium Species: Isolation, Structural Elucidation, Total Synthesis, and Bioactivity.

Kozupeptins A and B, novel antimalarial lipopeptides, were isolated from the culture broths of Paracamarosporium sp. FKI-7019. They exhibited potent antimalarial activity against chloroquine-sensitive and -resistant Plasmodium falciparum strains in vitro.

Ceratinadins E and F, New Bromotyrosine Alkaloids from an Okinawan Marine Sponge sp.

Two new bromotyrosine alkaloids, ceratinadins E () and F (), were isolated from an Okinawan marine sponge sp. as well as a known bromotyrosine alkaloid, psammaplysin F (). The gross structures of and were elucidated on the basis of spectroscopic data.

Peyer's patch-immunomodulating glucans from sugar cane enhance protective immunity through stimulation of the hemopoietic system.

The aim of the present study was chemical clarification of in vitro Peyer's patch-immunomodulating polysaccharides in sugar cane molasses, and evaluation of in vivo modulating activity on immune function of T lymphocytes in Peyer's patches and on microenvironment of hemopoietic system. Five kinds of glucans, comprising of dextranase-sensitive and activity-related d-glucosyl moieties, were purified as in vitro Peyer's patch-immunomodulating polysaccharides from the molasses. Oral administration of a glucan-enriched subfraction induced IL-2 and GM-CSF-producing T lymphocytes in Peyer's patches, resulting in enhancement of IL-6 production in a hemopoietic microenvironment to boost neutrophil numbers in the peripheral blood stream.

Design and De Novo Synthesis of 6-Aza-artemisinins.

Development of designer natural product variants, 6-aza-artemisinins, enabled us to achieve structural modification of the hitherto unexplored cyclohexane moiety of artemisinin and concise de novo synthesis of the tetracyclic scaffold in just four steps from the modular assembly of three simple building blocks. This expeditious catalytic asymmetric synthetic approach generated lead candidates exhibiting superior in vivo antimalarial activities to artemisinin.

Tolyprolinol, a new dipeptide from Tolypocladium sp. FKI-7981.

A new dipeptide, named tolyprolinol, was isolated from the static culture of a fungus, Tolypocladium sp. FKI-7981. The structure of tolyprolinol was elucidated as N-acetyl-L-phenylalanyl-L-prolinol.