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Volume 61, Issue 9
Displaying 1-13 of 13 articles from this issue
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Review
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Yoshio Hayashi, Yuri Yamazaki-Nakamura, Fumika Yakushiji2013 Volume 61 Issue 9 Pages 889-901
Published: September 01, 2013
Released on J-STAGE: September 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLCertain antimicrotubule agents displaying colchicine-like tubulin-depolymerizing activity can act as both cytotoxic and vascular-disrupting agents (VDAs). VDAs constitute a new class of anticancer drugs and are currently in clinical trials. We have developed a VDA clinical candidate (phase II) diketopiperazine (DKP)-type antimicrotubule agent called plinabulin (7) derived from the natural DKP phenylahistin (5), which displays colchicine-like tubulin-depolymerizing activity. To develop more potent antimicrotubule DKP derivatives, we performed an intensive structure–activity relationship study examining the phenyl group of compound 7. This study identified more potent DKP derivatives (2,5-difluoro derivatives [29] and benzophenone derivatives [36]) with vascular-disrupting activities. The benzophenone moiety of compound 36 was further modified to yield the most potent cytotoxic derivative yet discovered, the 4-fluorobenzophenone derivative 38m, which inhibited the growth of HT-29 cells in vitro at subnanomolar levels. As both VDAs and cytotoxic agents, these potent DKP derivatives are valuable second-generation drug candidates. The chemical biology of plinabulin was examined by designing and synthesizing biotin-tagged photoaffinity probes 40–42 that could be used to indicate the binding mode of compound 7 with tubulin. A tubulin photoaffinity labeling study suggested that compound 7 binds at the interface between the α- and β-tubulins near the colchicine-binding site and not inside the colchicine-binding cavity. A water-soluble prodrug of the poorly water-soluble 7 was next designed in an effort to improve the pharmacokinetics and chemotherapeutic indices. The lead compound 56 revealed high water solubility and a half-life profile appropriate for an injected drug.View full abstractDownload PDF (5657K) Full view HTML
Regular Articles
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Hiraku Onishi, Mototaka Matsuyama2013 Volume 61 Issue 9 Pages 902-912
Published: September 01, 2013
Released on J-STAGE: September 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLA conjugate between prednisolone (PD) and chondroitin sulfate (CS) with glycine as a linker was prepared in order to obtain an effective macromolecular prodrug against inflammatory disease, especially rheumatoid arthritis. First, PD was converted to the N-trityl-glycine ester (Tr-GP), and the glycine ester of PD (GP) was obtained by detritylation of Tr-GP. Then, GP and CS were condensed with water-soluble carbodiimide to yield CS-GP. The obtained conjugate had a PD content of 2.24% (w/w). Conversion characteristics were investigated for GP and CS-GP to evaluate their potential as a prodrug. In the stability test of GP, PD was released well in the buffer at pH 6–7.4, but degraded rapidly at pH 8 without sufficient release of PD. As to CS-GP, PD was released more slowly than in GP, and the release rate rose with the increase in the medium pH. PD was released gradually from CS-GP over 24 h at a physiological pH. The conversion profiles of both GP and CS-GP almost followed pseudo-first order kinetics. The calculated conversion rate constants supported the gradual and effective release from CS-GP. The release rate of PD from GP and CS-GP was accelerated by the addition of rat plasma, but the promotion of release from CS-GP was small, suggesting that PD should be released gradually from CS-GP in the systemic circulation. It was demonstrated from the preliminary pharmacological study using rats with adjuvant-induced arthritis that CS-GP had high anti-inflammatory potential against arthritis.View full abstractDownload PDF (1166K) Full view HTML -
Ivana Rašić Mišić, Gordana Miletić, Snežana Mitić, Milan Mitić, Emilij ...2013 Volume 61 Issue 9 Pages 913-919
Published: September 01, 2013
Released on J-STAGE: September 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLThe new kinetically-based spectrophotometric method for the determination of microquantities of ampicillin is proposed in the present paper. Ampicillin degradation in strong alkaline medium was applied for the method development. The reaction rate was monitored at 265 nm. A differential variation of the tangent method was used to process the kinetic data. The method is valid over the 3.49–55.84 µg/mL ampicillin concentration interval with relative standard deviation (RSD) range 7.79–3.20%. The calculated detection limit was determined at 2.58 µg/mL based on the 3.3S0 criterion. The interference effects of some metal ions, anions, amino acids and other molecules were investigated in order to assess the method selectivity. The method was successfully applied to determining the content of ampicillin in commercial pharmaceutical preparations and human urine. The obtained results were in good correlation with the HPLC method results. The newly developed method is simple, inexpensive and efficient for the analysis of a large number of samples at room temperature in a short time.View full abstractDownload PDF (753K) Full view HTML -
Gui-Hua Quan, Hee-Sung Chae, Hyuk Hwan Song, Kyoung-Seop Ahn, Hyeong-K ...2013 Volume 61 Issue 9 Pages 920-926
Published: September 01, 2013
Released on J-STAGE: September 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTML
Supplementary materialBioactivity-guided fractionation for an EtOAc-soluble fraction of methanolic extract of Arthraxon hispidus, using primary cell assay with bone marrow-derived mast cells (BMMC), led to an isolation of six new flavones and nine known compounds. The structures of the new compounds were established by one dimensional (1D)- and 2D-NMR spectroscopic data, as luteolin 8-C-β-kerriopyranoside (1), luteolin 8-acetic acid methyl ester (2), 7-methyl-luteolin 8-C-β-(6-deoxyxylo-3-uloside) (3), apigenin 8-C-α-fucopyranoside (4), apigenin 8-C-β-fucopyranoside (5) and luteolin 8-C-β-fucopyranoside (6). All the isolates were evaluated for inhibitory activities on interleukin-6 release in the primary cultures using BMMC. Of the tested compounds, compounds 2, 3 and 10 were found to inhibit interleukin-6 release. Furthermore, compound 2 displayed inhibitory activity against prostaglandin D2, leukotriene C4, and β-hexosaminidase releases.View full abstractDownload PDF (562K) Full view HTML -
Junichi Odo, Tomomi Hirashima, Tomoko Hayashida, Asuka Miyauchi, Mami ...2013 Volume 61 Issue 9 Pages 927-932
Published: September 01, 2013
Released on J-STAGE: September 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLThe catalysis of ascorbic acid (AsA) oxidation by anion-exchangers modified with metal complexes of thiacalix[4]arenetetrasulfonate (Me-TCAS[4]A-500, Me=Mn3+, Fe3+, Co3+, Ce4+, Cu2+, Zn2+, Ni2+, and H2) were investigated. Me-TCAS[4]A-500 (Me=Mn3+, Fe3+, Ce4+, and Cu2+) all exhibited the ability to catalyze the oxidative reaction of AsA to dehydroascorbic acid. However, in the presence of high concentrations of AsA, only Cu2+-TCAS[4]A-500 was capable of complete oxidation of the acid. Moreover, after six repeat uses, Cu2+-TCAS[4]A-500 maintained high and relatively constant catalytic activity. Prior treatment of glucose solutions with Cu2+-TCAS[4]A-500, even in the presence of high AsA concentrations, enabled the satisfactory determination of glucose without interference by AsA. Cu2+-TCAS[4]A-500 will therefore be applicable as an artificial substitute for ascorbate oxidase, and may be useful as a means to eliminate AsA interference during the analysis of vital compounds such as glucose and uric acid.View full abstractDownload PDF (626K) Full view HTML -
Nadia Abdalla Khalil, Eman Mohamed Ahmed, Khaled Omar Mohamed, Sawsan ...2013 Volume 61 Issue 9 Pages 933-940
Published: September 01, 2013
Released on J-STAGE: September 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLA series of 2-substituted phenyl derivatives of nicotinic acid 4a–l were synthesized and evaluated for their analgesic and anti-inflammatory activities. Compounds including 2-bromophenyl substituent, 4a, c, and d, proved to display distinctive analgesic and anti-inflammatory activities in comparison to mefenamic acid as a reference drug. Compound 4c could be identified as the most biologically active member within this study with an interesting dual anti-inflammatory analgesic profile. Effect of the compounds 4a–l on the serum level of certain inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 was also determined.View full abstractDownload PDF (1303K) Full view HTML -
Jing Lu, Yuanyuan Xie, Yao Tan, Jialin Qu, Hisashi Matsuda, Masayuki Y ...2013 Volume 61 Issue 9 Pages 941-951
Published: September 01, 2013
Released on J-STAGE: September 01, 2013
Advance online publication: June 12, 2013JOURNAL FREE ACCESS FULL-TEXT HTML
Supplementary materialAn ultra performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight mass spectrometry (QTOF/MS) method is established for the rapid analysis of isoflavones, saponins and flavones in 16 samples originated from the flowers of Pueraria lobata and P. thomsonii. A total of 25 isoflavones, 13 saponins and 3 flavones were identified by co-chromatography of sample extract with authentic standards and comparing the retention time, UV spectra, characteristic molecular ions and fragment ions with those of authentic standards, or tentatively identified by MS/MS determination along with Mass Fragment software. Moreover, the method was validated for the simultaneous quantification of 29 components. The samples from two Pueraria flowers significantly differed in the quality and quantity of isoflavones, saponins and flavones, which allows the possibility of showing their chemical distinctness, and may be useful in their standardization and quality control. Dataset obtained from UPLC-MS was processed with principal component analysis (PCA) and orthogonal partial least squared discriminant analysis (OPLS-DA) to holistically compare the difference between both Pueraria flowers.View full abstractDownload PDF (860K) Full view HTML -
Kousuke Akiyama, Tomoko Mineno, Masafumi Okawa, Junei Kinjo, Hiroyuki ...2013 Volume 61 Issue 9 Pages 952-961
Published: September 01, 2013
Released on J-STAGE: September 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLTreatment of the ether-insoluble resin glycoside (convolvulin) fraction from seeds of Quamoclit pennata (Convolvulaceae) with indium(III) chloride in methanol provided three oligoglycosides of hydroxy fatty acid (glycosidic acid) methyl esters and two methyl glycosides, which were partially acylated by a glycosidic acid, 7S-hydroxydecanoic acid 7-O-β-D-quinovopyranoside (quamoclinic acid B) and/or two organic acids, (E)-2-methylbut-2-enoic (tiglic) acid and/or 3R-hydroxy-2R-methylbutyric (nilic) acid. Their structures were elucidated on the basis of spectroscopic data and chemical conversions.View full abstractDownload PDF (719K) Full view HTML -
Yohei Hoashi, Yuichi Tozuka, Hirofumi Takeuchi2013 Volume 61 Issue 9 Pages 962-966
Published: September 01, 2013
Released on J-STAGE: September 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLThe purpose of this study was to develop and test a novel and simple method for evaluating the disintegration time of rapidly disintegrating tablets (RDTs) in vitro, since the conventional disintegration test described in the pharmacopoeia produces poor results due to the difference of its environmental conditions from those of an actual oral cavity. Six RDTs prepared in our laboratory and 5 types of commercial RDTs were used as model formulations. Using our original apparatus, a good correlation was observed between in vivo and in vitro disintegration times by adjusting the height from which the solution was dropped to 8 cm and the weight of the load to 10 or 20 g. Properties of RDTs, such as the pattern of their disintegrating process, can be assessed by verifying the load. These findings confirmed that our proposed method for an in vitro disintegration test apparatus is an excellent one for estimating disintegration time and the disintegration profile of RDTs.View full abstractDownload PDF (744K) Full view HTML
Notes
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Takashi Isobe, Kyoko Kofuji, Yoshifumi Murata2013 Volume 61 Issue 9 Pages 967-970
Published: September 01, 2013
Released on J-STAGE: September 01, 2013
Advance online publication: July 11, 2013JOURNAL FREE ACCESS FULL-TEXT HTMLAlginic acid (Alg) is a natural anionic polysaccharide, which consists of α-L-guluronic acid (G) and β-D-mannuronic acid (M). G-G sequence-rich chain regions, known as G-blocks (GB), are important regions for gelation of Alg using divalent cations. In this study, calcium-induced GB gel beads were prepared, and drug release profiles and degradation properties of the GB gel beads were investigated in aqueous media. The GB gel beads swelled slightly in JP XVI 1st fluid (pH 1.2), and only slight release of sodium diclofenac (DF) from the GB gel beads was observed. Disintegration of the GB gel beads was not observed in the 1st fluid. On the other hand, the GB gel beads disintegrated in JP XVI 2nd fluid (pH 6.8), and the rate of disintegration depended on the concentration of calcium chloride used to prepare the GB gel beads. The DF release profiles of the GB gel beads in the 2nd fluid could be controlled by the concentration of CaCl2 used to prepare the GB gel beads. The initial release profile of DF from GB gel beads was not consistent with the profile of disintegration. According to the Higuchi-plot of the percentage of drug content released against the square root of time, gel disintegration did not affect the release of DF from GB gel beads. It appears that a diffusion-type mechanism was responsible for DF release. We propose that the GB gel bead gel matrix is an effective medium by which to control the release of drug within the gastrointestinal tract.View full abstractDownload PDF (417K) Full view HTML -
Joo Young Lee, Ju Sun Kim, Yeong Shik Kim, Sam Sik Kang2013 Volume 61 Issue 9 Pages 971-978
Published: September 01, 2013
Released on J-STAGE: September 01, 2013
Advance online publication: June 21, 2013JOURNAL FREE ACCESS FULL-TEXT HTMLAn investigation of the Korean medicinal plant Patrinia villosa (THUNB.) JUSS. (Valerianaceae) led to the isolation of two new flavonoid glycosides, patrivilosides 1 (1) and 2 (2), a new iridoid glycoside, patrinovalerosidate (3), and two new saponins, patrinovilosides A (4) and B (5), along with six known compounds including three flavonoid glycosides and three iridoid glycosides. The structures of the new compounds were elucidated based on analysis of their one dimensional (1D)- and 2D-NMR spectra along with their mass spectrometric data and the results of acid hydrolysis.View full abstractDownload PDF (592K) Full view HTML -
Hiroyuki Fuchino, Fumiyuki Kiuchi, Azusa Yamanaka, Akihiro Obu, Hirosh ...2013 Volume 61 Issue 9 Pages 979-982
Published: September 01, 2013
Released on J-STAGE: September 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLTwo new stilbenes, 1 and 2, were isolated as leishmanicidal constituents from the methanolic extract of Lonchocarpus nicou leaves and stem, together with five known stilbenes and rotenoids. Their chemical structures were determined by spectral methods. Among them, the cis stilbene-type compounds 1 and 4 showed potent leishmanicidal activity (IC50: 5.5, 3.9 µg/mL), while the trans stilbene-type compounds 2 and 5, and rotenoids 6 and 7, showed moderate activities (IC50: 9.9, 12.8, 22.6, 19.6 µg/mL, respectively).View full abstractDownload PDF (409K) Full view HTML -
Guanguan Qiu, Pengcheng Yan, Weiwei Shao, Jie Zhou, Weiwei Lin, Liangl ...2013 Volume 61 Issue 9 Pages 983-986
Published: September 01, 2013
Released on J-STAGE: September 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLTwo new sesquiterpenoids, namely elema-1,3,7(11),8-tetraen-8,12-lactam (1) and 7β,8α-dihydroxy-1α,4αH-guai-9,11-dien-5β,8β-endoxide (2), together with five known analogs were isolated from the EtOAc extract of the rhizomes of Curcuma wenyujin. Their structures and relative configurations were determined on the basis of spectroscopic methods including 2D-NMR techniques. All compounds were tested for the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Compound 1 showed the significant inhibitory activity with IC50 values of 9.4 µM.View full abstractDownload PDF (558K) Full view HTML
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