著者

Yuto Kondo Seikou Nakamura Sayaka Ino Haruka Yamashita Souichi Nakashima Masayuki Yamashita Hisashi Matsuda

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.68, no.6, pp.520-525, 2020-06-01 (Released:2020-06-01)

参考文献数

22

被引用文献数

4 5

---

An asymmetric nitrogen-containing dimer, leiocarpanine A, was isolated from the aerial part of Mercurialis leiocarpa as a new compound. The new generation process of leiocarpanine A was estimated and a concise synthesis of leiocarpanine A could be detailed based on mimicking the generation process through the radical intermediates. In general, a lot of reaction step and organic reagents are required for the synthesis of asymmetric nitrogen-containing dimers. However, our new synthesis method enables a concise synthesis of asymmetric nitrogen-containing dimers through radical intermediates by only liquid-separation. This synthetic method provides a rapid and concise pathway to construct a library of nitrogen-containing dimers that might be useful for drug discovery. In addition, it is useful to elucidate the generation process of leiocarpanine A.

著者

Keiji Nishiwaki Shinya Nakamura Kenji Yoshioka Eri Nakagawa Shiori Nakatani Masato Tsuyuguchi Takayoshi Kinoshita Isao Nakanishi

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.71, no.7, pp.558-565, 2023-07-01 (Released:2023-07-01)

参考文献数

47

---

Protein kinase CK2 (CK2) is involved in the suppression of gene expression, protein synthesis, cell proliferation, and apoptosis, thus making it a target protein for the development of therapeutics toward cancer, nephritis, and coronavirus disease 2019. Using the solvent dipole ordering-based method for virtual screening, we identified and designed new candidate CK2α inhibitors containing purine scaffolds. Virtual docking experiments supported by experimental structure–activity relationship studies identified the importance of the 4-carboxyphenyl group at the 2-position, a carboxamide group at the 6-position, and an electron-rich phenyl group at the 9-position of the purine scaffold. Docking studies based on the crystal structures of CK2α and inhibitor (PDBID: 5B0X) successfully predicted the binding mode of 4-(6-carbamoyl-8-oxo-9-phenyl-8,9-dihydro-7H-purin-2-yl) benzoic acid (11), and the results were used to design stronger small molecule targets for CK2α inhibition. Interaction energy analysis suggested that 11 bound around the hinge region without the water molecule (W1) near Trp176 and Glu81 that is frequently reported in crystal structures of CK2α inhibitor complexes. X-ray crystallographic data for 11 bound to CK2α was in very good agreement with the docking experiments, and consistent with activity. From the structure–activity relationship (SAR) studies presented here, 4-(6-Carbamoyl-9-(4-(dimethylamino)phenyl)-8-oxo-8,9-dihydro-7H-purin-2-yl) benzoic acid (12) was identified as an improved active purine-based CK2α inhibitor with an IC50 of 4.3 µM. These active compounds with an unusual binding mode are expected to inspire new CK2α inhibitors and the development of therapeutics targeting CK2 inhibition.

著者

Keiko Ogawa Daiki Sakamoto Rumiko Hosoki

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.71, no.7, pp.486-494, 2023-07-01 (Released:2023-07-01)

参考文献数

96

被引用文献数

1

---

Computational approaches to drug development are rapidly growing in popularity and have been used to produce significant results. Recent developments in information science have expanded databases and chemical informatics knowledge relating to natural products. Natural products have long been well-studied, and a large number of unique structures and remarkable active substances have been reported. Analyzing accumulated natural product knowledge using emerging computational science techniques is expected to yield more new discoveries. In this article, we discuss the current state of natural product research using machine learning. The basic concepts and frameworks of machine learning are summarized. Natural product research that utilizes machine learning is described in terms of the exploration of active compounds, automatic compound design, and application to spectral data. In addition, efforts to develop drugs for intractable diseases will be addressed. Lastly, we discuss key considerations for applying machine learning in this field. This paper aims to promote progress in natural product research by presenting the current state of computational science and chemoinformatics approaches in terms of its applications, strengths, limitations, and implications for the field.

著者

Kazuhisa Sugimoto Takahisa Nishimura Koji Nomura Kenji Sugimoto Takashi Kuriki

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.51, no.7, pp.798-801, 2003 (Released:2003-07-01)

参考文献数

16

被引用文献数

103 110

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The effects of 4-hydroxyphenyl α-glucopyranoside (α-arbutin) and 4-hydroxyphenyl β-glucopyranoside (arbutin) on the activity of tyrosinase from human malignant melanoma cells were examined. The inhibitory effect of α-arbutin on human tyrosinase was stronger than that of arbutin. The Ki value for α-arbutin was calculated to be 1/20 that for arbutin. We then synthesized arbutin-α-glycosides by the transglycosylation reaction of cyclomaltodextrin glucanotransferase using arbutin and starch, respectively, as acceptor and donor molecules. The structural analyses using 13C- and 1H-NMR proved that the transglycosylated products were 4-hydroxyphenyl β-maltoside (β-Ab-α-G1) and 4-hydroxyphenyl β-maltotrioside (β-Ab-α-G2). These arbutin-α-glycosides exhibited competitive type inhibition on human tyrosinase, and their Ki values were calculated to be 0.7 mM and 0.9 mM, respectively. These arbutin-α-glycosides posessed stronger inhibitory activity than arbutin, but less activity than α-arbutin. These results suggested that the α-glucosidic linkage of hydroquinone-glycosides plays an important role in the inhibitory effect on human tyrosinase.

著者

Naoyuki Toriumi Atsuya Muranaka Masanobu Uchiyama

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.71, no.6, pp.459-461, 2023-06-01 (Released:2023-06-01)

参考文献数

19

---

Organic compounds with near-IR (NIR) fluorescence have many potential applications in materials and life sciences, but the much weaker intensity of fluorescence in the NIR region than in the UV-visible region is a major obstacle. Herein we show that deuteration of phthalocyanines, a representative class of organic NIR dyes, increases both the fluorescence quantum yield and the fluorescence lifetime compared with non-deuterated phthalocyanines.

著者

Lingjia Gu Qian Gao Liansong Ni Meirong Wang Feixia Shen

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.61, no.7, pp.688-694, 2013-07-01 (Released:2013-07-01)

参考文献数

49

被引用文献数

34 34

---

Renal fibrosis is a crucial pathologic process underlying diabetic nephropathy (DN). Central to this process is the epithelial-mesenchymal transformation (EMT) of tubular epithelial cells. Fasudil, a Rho-associated coiled-coil forming protein serine/threonine kimase (ROCK) inhibitor, protects against renal fibrosis in a variety of renal injury models. However, fasudil’s effects on renal fibrosis in DN remain unknown. The aim of the present study was to investigate the effects of fasudil on high glucose-induced EMT in human renal tubular epithelial (HK-2) cells. HK-2 cells were exposed to 5.5 or 60 mmol/L D-glucose for 72h, or to mannitol (osmotic control). RhoA activity was assessed using a RhoA pull-down assay, and ROCK activity was determined by myosin phosphatase target subunit-1 (MYPT1) phosphorylation. Myofibroblast (vimentin and α-smooth muscle actin [α-SMA]) and epithelial (E-cadherin) markers expressions were detected by immunocytochemistry and Western blotting. Transforming growth factor (TGF)-β1 and fibronectin secretion were detected with enzyme-linked immunosorbent assay (ELISA), and connective tissue growth factor (CTGF) was analyzed by Western blotting. Results showed that high glucose levels induced morphological changes, reduced E-cadherin expression (−73%), increased expression of vimentin (+148%) and α-SMA (+226%), increased TGF-β1 (from 116.0±5.2 µg/g to 351.0±3.2 µg/g) and CTGF (from 0.26±0.01 to 0.92±0.03) secretion, and increased RhoA and ROCK activation (p<0.05 for all). All these effects of high glucose stimulation were suppressed or abolished by fasudil. In conclusion, fasudil may attenuate EMT through reduced activation of RhoA/ROCK signaling, and decreased expression of TGF-β1 and CTGF. Thus, fasudil may be a renoprotective agent for the treatment of DN.

著者

Kazunori Miwa Yan Guo Masayuki Hata Norio Yamamoto Tyuji Hoshino

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.71, no.5, pp.360-367, 2023-05-01 (Released:2023-05-01)

参考文献数

39

被引用文献数

3

---

Computational screening is one of the fundamental techniques in drug discovery. Each compound in a chemical database is bound to the target protein in virtual, and candidate compounds are selected from the binding scores. In this work, we carried out combinational computation of docking simulation to generate binding poses and molecular mechanics calculation to estimate binding scores. The coronavirus infectious disease has spread worldwide, and effective chemotherapy is strongly required. The viral 3-chymotrypsin-like (3CL) protease is a good target of low molecular-weight inhibitors. Hence, computational screening was performed to search for inhibitory compounds acting on the 3CL protease. As a preliminary assessment of the performance of this approach, we used 51 compounds for which inhibitory activity had already been confirmed. Docking simulations and molecular mechanics calculations were performed to evaluate binding scores. The preliminary evaluation suggested that our approach successfully selected the inhibitory compounds identified by the experiments. The same approach was applied to 8820 compounds in a database consisting of approved and investigational chemicals. Hence, docking simulations, molecular mechanics calculations, and re-evaluation of binding scores including solvation effects were performed, and the top 200 poses were selected as candidates for experimental assays. Consequently, 25 compounds were chosen for in vitro measurement of the enzymatic inhibitory activity. From the enzymatic assay, 5 compounds were identified to have inhibitory activities against the 3CL protease. The present work demonstrated the feasibility of a combination of docking simulation and molecular mechanics calculation for practical use in computational virtual screening.

著者

Makoto Oba Mika Shibuya Yuto Yamaberi Hidetomo Yokoo Satoshi Uchida Atsushi Ueda Masakazu Tanaka

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.71, no.3, pp.250-256, 2023-03-01 (Released:2023-03-01)

参考文献数

23

被引用文献数

3

---

Amphipathic peptides composed of cationic amino acids and hydrophobic amino acids have cell-penetrating ability and are often used as a delivery tool for membrane-impermeable compounds. Small interfering RNA (siRNAs) are one of the delivery targets for such cell-penetrating peptides (CPPs). Cationic CPPs can associate with anionic siRNAs by electrostatic interactions resulting in the formation of nano-sized complexes, which can deliver siRNAs intracellularly. CPPs containing unnatural amino acids offer promising tools to siRNA delivery. However, the detailed structure–activity relationship in siRNA delivery has been rarely studied. In the current study, we designed peptides containing dipropylglycine (Dpg) and explored the cellular uptake and cytotoxicity of peptide/siRNA complexes. The amphipathic structure of the peptides played a key role in complexation with siRNAs and intracellular siRNA delivery. In the amphipathic peptides, cellular uptake of siRNA increased with increasing peptide length, but cytotoxicity was reduced. A peptide containing four Dpg exhibited an effective gene-silencing effect with small amounts of peptides without cytotoxicity in medium containing serum. These findings will be helpful for the design of novel CPPs for siRNA delivery.

著者

Rio Uno Kyoko Ohkawa Honami Kojima Tamami Haraguchi Minoru Ozeki Ikuo Kawasaki Miyako Yoshida Masaaki Habara Hidekazu Ikezaki Takahiro Uchida

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.71, no.2, pp.148-153, 2023-02-01 (Released:2023-02-01)

参考文献数

23

被引用文献数

1

---

This study aimed to evaluate the bitterness of famotidine (FAM) combined with each of three non-steroidal anti-inflammatory drugs (NSAIDs): ibuprofen (IBU), flurbiprofen (FLU), and naproxen (NAP), which have potential as fixed-dose combination (FDC) drugs. We evaluated the bitterness of FAM and each NSAID by taste sensor AN0 and C00, respectively. FAM showed high sensor output representing sensitivity to bitterness, whereas three NSAIDs did not show large sensor output, suggesting that the bitterness intensities of three NSAIDs were lower than that of FAM. The bitterness of FAM on sensor AN0 was suppressed in a concentration-dependent manner when mixed with IBU, FLU, or NAP. Among three NSAIDs, IBU most effectively inhibited bitterness on sensor output, and the gustatory sensation test confirmed that adding IBU to FAM reduced the bitterness of FAM in a concentration-dependent manner. MarvinSketch confirmed that the drugs were mostly present in an ionic solution when FAM was mixed with NSAIDs. The 1H-NMR spectroscopy analysis also revealed the presence of electrostatic interactions between FAM and NSAIDs, suggesting that the electrostatic interaction between FAM and NSAIDs might inhibit the adsorption of FAM on the bitter taste sensor membrane, thereby masking the bitter taste.

著者

Tatsuo Akaki Shinya Nakamura Keiji Nishiwaki Isao Nakanishi

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

pp.c22-00866, (Released:2023-02-02)

参考文献数

52

---

The fragment molecular orbital (FMO) method is a fast quantum-mechanics method that divides systems into pieces of fragments and performs ab initio calculations. The method has been expected to improve the accuracy of describing protein-ligand interactions by incorporating electronic effects. In this article, FMO calculation with solvation methods were applied to the affinity prediction at the ATP-binding site of PDHK4. As the ionized aspartic acid lies at the center and is involved in the complex hydrogen bond networks, this system has turned out to be a difficult target to describe by traditional molecular-mechanics method. In the FMO calculation with the polarizable continuum model (PCM) solvation method, a considerable amount of charge (-0.27e) was transferred from the ionized aspartate to the surrounding residues. We found that using FMO with the PCM solvation method was important to increase the correlation, and by incorporating the ligand deformation energy, the correlation was improved to R = 0.81 for whole twelve compounds and R= 0.91 without one outlier compound.

著者

平林 一広 岩田 進 松本 広淳 森 武雄 柴田 承二 馬場 昌範 伊藤 正彦 茂田 士郎 中島 秀喜 山本 直樹

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.39, no.1, pp.112-115, 1991-01-25 (Released:2008-03-31)

参考文献数

15

被引用文献数

67 79

---

Chemically modified compounds of glycyrrhizin have been synthesized and evaluated for their inhibitory effect on the replication of human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 1 (HSV-1). Among them, the 11-deoxo compound having a heteroannular diene structure at the C and D rings proved as active against HIV-1 as glycyrrhizin in MT-4 and MOLT-4 cells. It completely inhibited HIV-1-induced cytopathogenicity in both cell lines at a concentration of 0.16mM. The compound was also effective against HSV-1 with a 50% inhibitory concentration of 0.5μM.

著者

Tadahiro TAKEDA Ryoko GONDA Keiichiro HATANO

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.45, no.4, pp.697-699, 1997-04-15 (Released:2008-03-31)

参考文献数

7

被引用文献数

21 23

---

Three aromatic glycosides, lucumin, lucuminamide and lucuminic acid, were isolated from the seeds of Calocarpum sapota MERRILL (Sapotaceae). Their structures were established by spectroscopic methods, chemical evidence, and X-ray crystallography.

著者

山根 靖弘 斉藤 静男 小泉 利明

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.31, no.9, pp.3214-3221, 1983-09-25 (Released:2008-03-31)

参考文献数

34

被引用文献数

1 2

---

The cooperative inhibitory action of heparin and antithrombin III on the thrombinfibrinogen reaction was neutralized by preincubating these anticoagulant factors in the presence of Ca or Mg, and the effect was larger with Ca than with Mg. However, the neutralizing action of Ca decreased in the presence of Mg. Bindings of poly-L-lysine and antithrombin III to heparin were also inhibited by the addition of Ca and Mg, and Ca had a larger effect than Mg. On the other hand, the binding ability of Ca to heparin was larger than that of Mg, and the coexistence of these metals reduced the binding affinity of each metal. These data suggest that the neutralizing action of Ca and Mg on the anticoagulant action of heparin and antithrombin III may be related to the ability of these metals to prevent the complex formation of the acid mucopolysaccharide and the thrombin inhibitor by binding to the acid mucopolysaccharide.

著者

Hirotaka Murase Jeongsu Lee Yosuke Taniguchi Shigeki Sasaki

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.71, no.1, pp.64-69, 2023-01-01 (Released:2023-01-01)

参考文献数

16

---

In nucleic acid drug discovery, it is extremely important to develop a technology to understand the distribution in target organs and to trace the degradation process in the body in order to optimize the structure and improve the efficiency of the clinical trial process. Since nucleic acid drugs are essentially metabolically degraded into numerous fragments, labeling at the internal position is preferable to that at the terminus. Due to the high molar specific activity of tritium, various approaches for tritium-labeling have been studied for nucleic acid drugs. Nevertheless, a generally-applicable method for tritium labeling of the internal position of a nucleic acid has not been established. In this study, we have demonstrated a new and efficient method for site-specific tritium labeling of the cytosine base at a predefined internal position in nucleic acid drugs. This method was developed by the chemical modification of the cytosine 4-amino group with the pyridinyl vinyl keto group by the functionality-transfer reaction using the reactive oligodeoxynucleotide (ODN), followed by reduction with NaBT4. Applicability to a variety of chemical structures, such as 5-methyl cytosine, 2′-O-methyl, 2′-fluoro ribose derivatives, Locked/Bridged nucleic acid (LNA/BNA) derivatives, as well as phosphorothioate bonds, has been evidenced using nine oligoribonucleic acid (ORN) substrates. It has been clearly demonstrated that this method is an excellent method for tritium-labeling of nucleic acid with an average conversion efficiency of 74%, an average isolated labeling yield of 60%, and an average specific activity of 61 GBq/mmol. This method is expected to contribute to the preclinical absorption, distribution, metabolism, excretion (ADME) studies of nucleic acid drug candidates.

著者

Yoshinori Ueno Ryuichiro Suzuki Masashi Kitamura

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.12, pp.859-862, 2022-12-01 (Released:2022-12-01)

参考文献数

10

被引用文献数

3

---

The root of Paeonia lactiflora (PAEONIAE RADIX) is a constituent of the traditional Japanese medicines (Kampo) and is known to have various effects. Peony roots cultivated in Japan and China are available in the Japanese market for medicinal use. In this study, the chemical diversity of ten available peony roots in the market that differed in their cultivation area was investigated using 1H-NMR metabolomics techniques. Principal component analysis and hierarchical cluster analysis of the 1H-NMR spectra of the peony roots methanolic extracts revealed a clear difference between the metabolic profiles of Japanese and Chinese peony roots. By preparative procedures using chromatography based on 1H-NMR spectra measurements, oxypaeoniflorin and (+)-catechin were found to be specific compounds for Japanese peony root. All peony roots used in this study were listed in the Japanese Pharmacopoeia. Therefore, the differences in the constituents of these peony roots might be attributed to growing conditions than differences in species. Cultivation conditions also influence the quality of natural medicines.

著者

Hiroyuki Fuchino Naoko Anjiki Sayaka Murase Hirotaka Matsuo Shigeki Hayashi Nobuo Kawahara Kayo Yoshimatsu

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.12, pp.848-858, 2022-12-01 (Released:2022-12-01)

参考文献数

18

---

In this study, we investigated the correlation between the cultivation conditions and chemical composition of Ephedra sinica and E. sp. (denoted EP-13, which has been grown at the National Institutes of Biomedical Innovation, Health, and Nutrition for many years). The total contents of ephedrine and pseudoephedrine are specified in the Japanese Pharmacopoeia; therefore, we investigated the changes in their content under different cultivation conditions, including varying soil conditions and fertilization or the lack of fertilization. Poor growth due to low soil nutrition and lack of sunlight caused decrease of the alkaloid content. As expected, the plants accumulated proline, although the proline content varied considerably with cultivation location. The proline concentration correlated with the content of methanoproline. Moreover, a new compound, namely N,N-dimethyl-p-hydroxyphenylethylamine-O-[β-D-glucopyranosyl-(1→3)-α-L-rhamnopyranoside], was isolated from E. sinica but was absent in EP-13. This study on the correlation between cultivation methods and the alkaloid content in Ephedra is expected to assist in the future production of quality Ephedra herb.

著者

Qi Zhang Peizheng Yan Pan Zhao Dongsheng Zhao Heran Cao Jing Lu Beibei Mao

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

pp.c22-00576, (Released:2022-11-26)

参考文献数

35

---

mTOR is an effective anti-tumor drug target. Several mTOR kinase inhibitors have entered clinical research, but there are still challenges of potential toxicity. As a new type of targeted drug, proteolysis targeting chimeras (PROTACs) have features of low dosage and low toxicity. However, this approach has been rarely reported to involve mTOR degradation. In this study, the mTOR kinase inhibitor MLN0128 was used as the ligand to the protein of interest and conjugated with pomalidomide by diverse intermediate linkage chains. Several potential small molecule PROTACs for the degradation of mTOR were designed and synthesized. PROTAC compounds exhibited mTOR inhibitory activity and suppressed MCF-7 cell proliferation. The representative compound P1 could inhibit the expression of mTOR downstream proteins and the growth of cancer cells by inducing autophagy but not affecting the cell cycle and not inducing apoptosis.

著者

鈴木 久美子 藤本 治宏 山崎 幹夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.31, no.6, pp.2176-2178, 1983-06-25 (Released:2008-03-31)

参考文献数

13

被引用文献数

10 17

---

Fasciculol E and F were identified as the toxic principles of Naematoloma fasciculare (Nigakuritake), a poisonous mushroom. These compounds caused paralysis and death in mice. The LD50 values of fasciculol E and F to mice were determined as 50 mg/kg and 168 mg/kg (i. p.), respectively.

著者

Takuya Murai Shohei Hamada Yusuke Kobayashi Takahiro Sasamori Takumi Furuta

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.9, pp.605-615, 2022-09-01 (Released:2022-09-01)

参考文献数

31

被引用文献数

1

---

The preparation, optical resolution, and structural investigations of a series of axially chiral biaryl dicarboxylic acids bearing oxygen, sulfur, and selenium atoms were carried out. The crystal structures of sulfur- and selenium-containing derivatives revealed that the carboxy groups of these compounds are located in a co-planar geometry with the fused aromatic rings including the chalcogen atoms. These conformational controls were found to be achieved by chalcogen-bonding interactions between chalcogen atoms in the aromatic rings and oxygen atoms in the carboxy groups. Even in the case of a binaphthofuran derivative, in which the formation of chalcogen-bonding interactions was expected to be negligible, the carboxy groups were also found to be located in a co-planar geometry toward its fused cyclic rings. Natural bond orbital (NBO) analyses of these dicarboxylic acids indicated the formation not only for the chalcogen-bonding interactions for S and Se derivatives, but also the tetrel-bonding interactions between the oxygen atoms in the carboxy groups and the carbon atoms in the fused cyclic rings for all biaryl dicarboxylic acids. These tetrel-bonding interactions were thought to contribute to conformational control in the binaphthofuran derivative. Physical and chiroptical properties such as the racemization barriers and circular dichroism (CD) spectra of these biaryl dicarboxylic acids were also revealed.

著者

三村 務 前田 和宏 辻坊 裕 佐竹 幹雄 藤田 孝夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.30, no.4, pp.1508-1512, 1982-04-25 (Released:2008-03-31)

参考文献数

11

被引用文献数

5 5

---

Octopus melanin obtained from ink bags of Octopus vulgaris CUVIER was found to inhibit gastric secretion in rats in the same way as that from Ommastrephes bartrami LESUEL. The molecular weight of this melanin fraction (which has an indole skeleton) was estimated to be over 200000 by gel filtration on Sephadex G-200, and the Octopus melanin fraction (Fr. OM) released several kinds of proteins in the presence of SDS. The chemical composition of Fr. OM was melanin pigment 79%, protein 17.5% and sugar 1.7%, so Fr. OM was considered to be a melanoprotein. Fr. OM significantly reduced gastric secretion in rats at the dose of 1 mg/kg, i.p., and also prevented both ulcer formation in pylorusligated rats and aspirin-induced ulcer.