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Volume 63, Issue 8
Displaying 1-11 of 11 articles from this issue
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Review
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Daisuke Urabe2015 Volume 63 Issue 8 Pages 565-572
Published: August 01, 2015
Released on J-STAGE: August 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLThis review summarizes the efforts to develop a radical-mediated three-component reaction and its application to a convergent approach to synthesize the 5/7/6-tricyclic framework (ABC-rings) of the densely functionalized dephnane diterpene, resiniferatoxin. The α-alkoxy bridgehead radical species, which was designed as the radical donor of the three-component reaction, was generated from O,Se- and O,Te-acetals under two different conditions. The generated α-alkoxy bridgehead radical effectively underwent the three-component reaction with α,β-unsaturated ketones and allyltributyltin/aldehyde under each of the conditions, giving rise to a wide variety of multiply functionalized 2,3-trans disubstituted cyclopentenone moieties. One of the established reactions was utilized as the key assembling reaction of the ABC-tricyclic framework of resiniferatoxin. The reaction of the bridgehead radical of the highly functionalized 6-membered C-ring, the 5-membered A-ring, and an allyltributyltin derivative effectively produced the C4-branched AC-rings. The last B-ring was constructed from the coupling adduct in two steps through the 7-endo cyclization, delivering the tricyclic framework possessing the correct C8 and 9-stereocenters of resiniferatoxin. The present methods demonstrate the power of the three-component reaction using an α-alkoxy bridgehead radical in a convergent approach to the complex architectures of daphnane diterpenes.Graphical Abstract Fullsize ImageView full abstractDownload PDF (1217K) Full view HTML
Regular Articles
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Jee Hee Suh, Eul Kgun Yum, Young Sik Cho2015 Volume 63 Issue 8 Pages 573-578
Published: August 01, 2015
Released on J-STAGE: August 01, 2015
Advance online publication: June 03, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLWe describe the synthesis and biological evaluation of N-aryl-5-aryloxazol-2-amine derivatives that are able to inhibit 5-lipoxygenase (5-LOX), a key enzyme of leukotriene synthesis, for the treatment of inflammation-related diseases including asthma and rheumatoid arthritis. A novel structural moiety containing oxazole was initially identified from a chemical library using an in vitro enzymatic and cell-based assay, and its synthesized oxazole derivatives were further examined to develop a structure–activity relationship (SAR). SAR analysis demonstrated that a hydroxyl or amino group at the p-position on N-phenyl was essential for the 5-LOX-inhibitory activities of the derivatives, and that other halogen and methyl group-substituted derivatives affected the potency, positively or negatively. As a result, derivatives selected through first-round screening were further optimized using a cell-based assay and an in vivo assay to develop a potent, selective 5-LOX inhibitor. A final hit exhibited an improved efficacy in arachidonic acid-induced ear edema when applied topically but not orally. Moreover, it showed the additional advantage of sustainable antiinflammatory activity over a reference compound, zileuton. Taken together, chemical entities bearing an oxazole scaffold could be promising as therapeutic drugs for the treatment of chronic inflammatory skin disorders.Graphical Abstract Fullsize ImageView full abstractDownload PDF (438K) Full view HTML -
Julie Rakel Mikell, Wimal Herath, Ikhlas Ahmad Khan2015 Volume 63 Issue 8 Pages 579-583
Published: August 01, 2015
Released on J-STAGE: August 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTML
Supplementary material6-Hydroxyflavanone (1) when fermented with fungal culture Cunninghamella blakesleeana (ATCC 8688a) yielded flavanone 6-O-β-D-glucopyranoside (2), flavanone 6-sulfate (3), and 6-hydroxyflavanone 7-sulfate (4). Aspergillus alliaceus (ATCC 10060) also transformed 1 to metabolite 3 as well as 4′-hydroxyflavanone 6-sulfate (5) and 6,4′-dihydroxyflavanone (6). Beauveria bassiana (ATCC 7159) metabolized 1 to 6 and flavanone 6-O-β-D-4-O-methyglucopyranoside (7). Mucor ramannianus (ATCC 9628) transformed 1 to 2,4-cis-6-hydroxyflavan-4-ol (8), 2,4-trans-6-hydroxyflavan-4-ol (9), 2,4-trans-6,4′-dihydroxyflavan-4-ol 5-sulfate (10), 1,3-cis-1-methoxy-1-(2,5-dihydroxyphenyl)-3-phenylpropane (11) and 2,4-trans-flavan-4-ol 6-sulfate (12). Structures of the metabolic products were elucidated by means of spectroscopic data. None of the metabolites tested showed antibacterial, antifungal and antimalarial activities against selected organisms. However, weak antileishmanial activity was observed for metabolite 11 when tested against Leishmania donovani.Graphical Abstract Fullsize ImageView full abstractDownload PDF (507K) Full view HTML -
Gautham Santhosh Kumar, Gaddameedi Jitender Dev, Nagiri Ravi Kumar, De ...2015 Volume 63 Issue 8 Pages 584-590
Published: August 01, 2015
Released on J-STAGE: August 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLA series of novel pyrido[1,2-a]pyrimidine-3-carboxamide derivatives 6a–n were prepared starting from 2(1H) pyridone 1 via hydrolysis, de-carboxylation, selective O-alkylation followed by rearrangement to give pyridine-2-amine 3. Compound 3 on reaction with ethoxy methylene malonic diethyl ester (EMME) under a conventional method followed by cyclization under micro wave irradiation (MWI) conditions resulted in product 5. Compound 5 on coupling with diverse substituted aliphatic amines formed title compounds 6a–n. All the products 6a–n were screened against four human cancer cell lines and compounds 6h–k and n which showed promising anticancer activity have been identified.Graphical Abstract Fullsize ImageView full abstractDownload PDF (478K) Full view HTML -
Yoshihiro Shibata, Katsuji Kagechika, Masahiro Ota, Mitsuhiro Yamaguch ...2015 Volume 63 Issue 8 Pages 591-602
Published: August 01, 2015
Released on J-STAGE: August 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLWe describe the design, syntheses, and structure–activity relationships of novel zwitterionic compounds as nonthiazolidinedion-based peroxisome proliferator-activated receptor (PPAR) α/γ dual agonists. In our previous report, we obtained compound 1 showing potent PPARα/γ dual agonistic activities, together with a sufficient glucose-lowering effect in db/db mice. However, this compound possessed an issue, i.e., the 1,3,4-oxadiazole ring was not stable in acidic conditions. Thus, we carried out further optimization to improve the stability while maintaining the other favorable profile features including potent PPARα/γ dual agonistic activity. We addressed the issue by changing the oxadiazole ring to a bioisostere amide group. These amide derivatives were stable in acidic conditions and decreased plasma glucose and plasma triglyceride levels significantly without marked weight gain.Graphical Abstract Fullsize ImageView full abstractDownload PDF (1371K) Full view HTML -
Zhi-Gang Sun, Xiao-Jing Zhou, Ming-Li Zhu, Wen-Ze Ding, Zhen Li, Hai-L ...2015 Volume 63 Issue 8 Pages 603-607
Published: August 01, 2015
Released on J-STAGE: August 01, 2015
Advance online publication: June 03, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLA series of aryl-2H-pyrazole derivatives were synthesized and evaluated for inhibitory activity against xanthine oxidase in vitro as potent xanthine oxidase inhibitors. Among them, 2 aryl-2H-pyrazole derivatives showed significant inhibitory activities against xanthine oxidase. Compound 19 emerged as the most potent xanthine oxidase inhibitor (IC50=9.8 µM) in comparison with allopurinol (IC50=9.5 µM). The docking study revealed that compound 19 might have strong interactions with the active site of xanthine oxidase. This compound is thus a new candidate for further development for the treatment of gout.Graphical Abstract Fullsize ImageView full abstractDownload PDF (763K) Full view HTML -
Yuka Uemura, Mio Iwami, Susumu Kawakami, Sachiko Sugimoto, Katsuyoshi ...2015 Volume 63 Issue 8 Pages 608-616
Published: August 01, 2015
Released on J-STAGE: August 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLFrom the leaves of Meliosma lepidota ssp. squamulata, megastigmane glucosides with spiro-structures and megastigmanes were isolated. Their structures were determined by X-ray crystallographic analyses and spectroscopic investigation. The absolute structures of the megastigmanes were determined by the modified Mosher’s method.Graphical Abstract Fullsize ImageView full abstractDownload PDF (1073K) Full view HTML
Notes
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Shinji Katsura, Nobuo Yamada, Atsushi Nakashima, Sumihiro Shiraishi, T ...2015 Volume 63 Issue 8 Pages 617-627
Published: August 01, 2015
Released on J-STAGE: August 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLThe aim of this study was to identify the chemical structure of the photodegradation products of furosemide in a water–acetonitrile mixture (1 : 1). Furosemide solution was irradiated with a D65 fluorescent lamp and the products were isolated by preparative HPLC. The fractions were evaporated to dryness in vacuo. The purity of the photodegradation products was measured by HPLC. The purity of products 1, 3, and 4 was greater than 90%, whereas that of product 2 was 13%, therefore, photodegradation product 2 was unstable. We identified photodegradation products 1 and 3 as 4-chloro-5-sulfamoylanthranilic acid and 4-hydroxy-N-furfuryl-5-sulfamoylanthranilic acid, respectively, by LC/MS and NMR. Additionally, we assumed that photodegradation product 4 was methyl 2-((furan-2-ylmethyl)amino)-4-hydroxy-3-(methyleneamino)-5-sulfamoylbenzoate by LC/MS and NMR. This showed that furosemide underwent hydrolysis and substitution, and reacted with the acetonitrile under the light of a D65 fluorescent lamp. We were furthermore able to determine the elution times of the photodegradation products of furosemide by applying the Japanese Pharmacopoeia chromatographic method for related substances to the isolated products.Graphical Abstract Fullsize ImageView full abstractDownload PDF (3987K) Full view HTML -
Siyun Nian, Xia Gan, Xiangduan Tan, Zhenpeng Yu, Panfeng Wang, Xing Ch ...2015 Volume 63 Issue 8 Pages 628-635
Published: August 01, 2015
Released on J-STAGE: August 01, 2015
Advance online publication: June 11, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLFourteen novel compounds were prepared and their antagonistic activities against liver X receptors (LXR) α/β were tested in vitro. Compound 26 had an IC50 value of 6.4 µM against LXRα and an IC50 value of 5.6 µM against LXRβ. Docking studies and the results of structure–activity relationships support the further development of this chemical series as LXRα/β antagonists.Graphical Abstract Fullsize ImageView full abstractDownload PDF (1363K) Full view HTML -
Nguyen Hoai Nam, Pham The Tung, Ninh Thi Ngoc, Tran Thi Hong Hanh, Ngu ...2015 Volume 63 Issue 8 Pages 636-640
Published: August 01, 2015
Released on J-STAGE: August 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTML
Supplementary materialTen biscembranoids (1–10), including the two new compounds sarcophytolides M and N (1 and 2), were isolated from the methanol extract of the Vietnamese soft coral Sarcophyton pauciplicatum. Their structures were elucidated by spectroscopic methods including one dimensional (1D)- and 2D-NMR, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and circular dichroism (CD). The in vitro cytotoxic activity of all isolated compounds against a panel of eight human cancer cell lines including HepG2 (hepatoma cancer), HL-60 (acute leukemia), KB (epidermoid carcinoma), LNCaP (prostate cancer), LU-1 (lung cancer), MCF7 (breast cancer), SK-Mel2 (melanoma), and SW480 (colon adenocarcinoma) was evaluated using the sulforhodamine B colorimetric assay. Among the isolated biscembranoids, 1, 3, 4, 7, 9, and 10 exhibited significant cytotoxic effects and may be selected for further studies of their anticancer activity.Graphical Abstract Fullsize ImageView full abstractDownload PDF (797K) Full view HTML -
Masateru Ono, Ayako Takigawa, Haruka Muto, Kiyotaka Kabata, Masafumi O ...2015 Volume 63 Issue 8 Pages 641-648
Published: August 01, 2015
Released on J-STAGE: August 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLFour new resin glycosides, named calysolins XIV (1), XV (2), XVI (3), and XVII (4) were isolated from the leaves, stems, and roots of Calystegia soldanella ROEM.. et SCHULT. (Convolvulaceae). Their structures were determined based on spectroscopic and chemical evidence, and consisted of two different types: those (1) with a macrolactone structure and those (2–4) with a non-macrolactone structure. Their sugar moieties were partially acylated by specific organic acids, including tiglic, 2S-methylbutyric, and 2S,3S-nilic acids. Additionally, evaluation of the antiviral activity of 1–4 revealed effects against the herpes simplex virus type 1.Graphical Abstract Fullsize ImageView full abstractDownload PDF (732K) Full view HTML
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