Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.chemphyslip.2020.104908

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.chemphyslip.2020.104871

PubMed

Language：English  

DOI： 10.1039/c9ra00229d

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Inc.  

Helicobacter pylori infects the human stomach and is closely linked with the development of gastric cancer. When detected, this pathogen can be eradicated from the human stomach using wide-spectrum antibiotics. However, year by year, H. pylori strains resistant to the antibacterial action of antibiotics have been increasing. The development of new antibacterial substances effective against drug-resistant H. pylori is urgently required. Our group has recently identified extremely selective bactericidal effects against H. pylori in (1R,3aR,7aR)-1-[(1R)-1,5-dimethylhexyl]octahydro-7a-methyl-4H-inden-4-one (VDP1) (otherwise known as Grundmann's ketone), an indene compound derived from the decomposition of vitamin D3 and proposed the antibacterial mechanism whereby VDP1 induces the bacteriolysis by interacting at least with PtdEtn (dimyristoyl-phosphatidylethanolamine [di-14:0 PtdEtn]) retaining two 14:0 fatty acids of the membrane lipid constituents. In this study, we synthesized new indene compounds ((1R,3aR,7aR)-1-((2R,E)-5,6-dimethylhept-3-en-2-yl)-7a-methyloctahydro-4H-inden-4-one [VD2-1], (1R,3aR,7aR)-1-((S)-1-hydroxypropan-2-yl)-7a-methyloctahydro-1H-inden-4-ol [VD2-2], and (1R,3aR,7aR)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-4-ol [VD3-1]) using either vitamin D2 or vitamin D3 as materials. VD2-1 and VD3-1 selectively disrupted the di-14:0 PtdEtn vesicles without destructing the vesicles of PtdEtn (dipalmitoyl-phosphatidylethanolamine) retaining two 16:0 fatty acids. In contrast, VD2-2, an indene compound lacking an alkyl group, had no influence on the structural stability of both PtdEtn vesicles. In addition, VD2-1 and VD3-1 exerted extremely selective bactericidal action against H. pylori without affecting the viability of commonplace bacteria. Meanwhile, VD2-2 almost forfeited the bactericidal effects on H. pylori. These results suggest that the alkyl group of the indene compounds has a crucial conformation to interact with di-14:0 PtdEtn of H. pylori membrane lipid constituents whereby the bacteriolysis is ultimately induced.

DOI： 10.1002/lipd.12043

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Pharmaceutical Society of Japan  

Reactive oxygen species (ROS) generated by reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox)1 mediate cellular signalings involved in normal physiological processes, and aberrant control of Nox1 has been implicated in the pathogenesis of various diseases. Therefore, Nox1 could have great potential as a therapeutic target. Here, we identified a novel Nox1 inhibitor, NOS31 secreted from Stretomyces sp. and analyzed its chemical structure. Furthermore, NOS31 was found to selectively inhibit Nox1-mediated ROS generation, with only a marginal effect on other Nox isoforms (Nox2–5) and no ROS scavenging activity. This compound blocked both Nox organizer 1 (NOXO1)/Nox activator 1 (NOXA1)-depen-dent and phorbol 12-myristate 13-acetate-stimulated Nox1-mediated ROS production in colon cancer cells. NOS31 inhibited the proliferation of several colon carcinoma and gastric cancer cell lines that upregulate the Nox1 system, whereas it had no appreciable effect on normal cells with low levels of Nox1. The finding suggests that NOS31 is a unique, potent Nox1 inhibitor of microbial origin and raises its possibility as a therapeutic agent for inhibiting gastrointestinal cancer cell growth.

DOI： 10.1248/bpb.b17-00804

Web of Science

Scopus

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley-VCH Verlag  

The development of new anchoring groups is important to facilitate effective co-sensitization in dye-sensitized solar cells (DSSCs). Herein, stable organic D–π–A dyes that contain new heterocyclic hydantoin-based anchoring groups have been designed, synthesized, and used in DSSCs. These dye sensitizers were evaluated in terms of their absorption spectra, electrochemical properties, and performance in DSSC devices. Although only one-third of the amount of hydantoin-containing dyes adsorbed onto TiO2 relative to their cyanoacrylic-acid-containing analogues, they exhibited effective photoexcited electron-transfer properties. External quantum efficiencies of over 80 % was observed, which were comparable to those of the cyanoacrylic-acid-containing dyes. In addition, the new hydantoin-containing dyes exhibited significant robustness, which could allow improved stability of their corresponding photovoltaic devices under harsh conditions, such as high temperature and humidity.

DOI： 10.1002/ajoc.201700542

Web of Science

Scopus

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Institute of Heterocyclic Chemistry  

A one-pot method for the synthesis of benzoxacycles including benzofuran, coumarin, benzoxazepine, and benzoxazocine from a common synthetic intermediate was established. Benzoxacycles are privileged structures in medicinal chemistry and have featured in several clinically used drugs. The synthesis of a benzofuran containing an aryl substituent was accomplished using potassium carbonate and sodium hydride. The one-pot synthesis of coumarin was also carried out using trans-decalin as the solvent. The optimized conditions for the one-pot synthesis of benzoxazepine can also be applied to the synthesis of benzoxazocine.

DOI： 10.3987/COM-17-13791

Web of Science

Scopus

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/ejoc.201402430

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/co200081j

Language：Japanese  

J-GLOBAL

Language：Japanese   Publisher：公益社団法人 日本薬学会  

フロー反応は，管内に試薬を流通させながら化学反応を行う手法であり，フラスコなどを用いるバッチ反応と比較して安全性，生産性に優れている．また，従来のフラスコ内でのかく拌とは異なり，微小空間において試薬を衝突させて混合を行うため，反応効率が向上することが知られている．一方で，反応の収率や選択性は反応器の形状(反応管の長さ，径，屈折など)に大きく依存するため，反応器の最適化が必要になり，簡便かつ目的に応じて反応器を微調整する工夫が必要である．3Dプリンターは，用途に合わせて迅速かつ自由自在に立体を造形でき，複雑な流路で構成されるフロー反応器の最適化において極めて効果的である．今回PuglisiとBenagliaらは，3Dプリンターで自作したフロー反応器を用い，医薬品原料として多用される光学活性1,2-アミノアルコール1の不斉合成に成功したので，本稿にて紹介する．<br>なお，本稿は下記の文献に基づいて，その研究成果を紹介するものである.<br>1) Movsisyan M. <i>et</i> <i>al</i>., <i>Chem</i>. <i>Soc</i>. <i>Rev</i>., <b>45</b>, 4892-4928(2016).<br>2) Rossi S. <i>et</i> <i>al</i>., <i>Angew</i>. <i>Chem</i>. <i>Int</i>. <i>Ed</i>., <b>56</b>, 4290-4294(2017).

Language：Japanese  

J-GLOBAL

Language：Japanese  

J-GLOBAL

Language：Japanese  

J-GLOBAL

Language：Japanese  

J-GLOBAL

Language：Japanese  

J-GLOBAL