著者

Atsushi Yamamoto Ko Nakamura Kazuhito Furukawa Yukari Konishi Takashi Ogino Kunihiko Higashiura Hisashi Yago Kaoru Okamoto Masanori Otsuka

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.50, no.1, pp.47-52, 2002 (Released:2002-03-19)

参考文献数

18

被引用文献数

21 32

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To find new tachykinin NK1 receptor antagonists from natural sources, we examined the tachykinin antagonist activity in the extracts of approximately 200 species of plants by the use of isolated guinea pig ileum. As a result, we discovered a novel and potent NK1 receptor antagonist in the extract of dried flowers of Matricaria chamomilla L. (chamomile). The structure of the antagonist was established as N1, N5, N10, N14-tetrakis[3-(4-hydroxyphenyl)-2-propenoyl]-1, 5, 10, 14-tetraazatetradecane (tetracoumaroyl spermine, 1a). The Ki values of 1a, estimated from the inhibitory action on the substance P (SP)-induced contraction of the guinea pig ileum and the inhibition of the binding of [3H][Sar9, Met(O2)11]SP to human NK1 receptors, were 21.9 nM and 3.3 nM, respectively. 1a is the first potent NK1 receptor antagonist from natural sources and it has a unique structure of a polyacylated spermine. 1a was concentrated in pollen of Matricaria chamomilla L. and was also found in the extracts of flowers of other four species of Compositae. In addition, we found N1, N5, N10-tris[3-(4-hydroxyphenyl)-2-propenoyl]-1, 5, 10, 14-tetraazatetradecane (2) as a new compound in the extract of flowers of Matricaria chamomilla L., which did not exhibit any tachykinin antagonist activity. A number of related compounds were synthesized, and the structure–activity relationship was studied.

著者

Mahitab Elsayed Daisuke Kobayashi Toshio Kubota Naoya Matsunaga Ryusei Murata Yuko Yoshizawa Natsuki Watanabe Tohru Matsuura Yuya Tsurudome Takashi Ogino Shigehiro Ohdo Takao Shimazoe

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.39, no.8, pp.1238-1246, 2016-08-01 (Released:2016-08-01)

参考文献数

64

被引用文献数

2 22

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Bisphosphonates and statins are known to have antitumor activities against different types of cancer cell lines. In the present study, we investigated the antiproliferative effects of the combination of zoledronic acid (ZOL), a bisphophosphonate, and fluvastatin (FLU), a statin, in vitro on two types of human pancreatic cancer cell lines, Mia PaCa-2 and Suit-2. The pancreatic cancer cell lines were treated with ZOL and FLU both individually and in combination to evaluate their antiproliferative effects using WST-8 cell proliferation assay. In this study, we demonstrated a potent synergistic antiproliferative effect of both drugs when used in combination in both cell lines. Moreover, we studied the molecular mechanism behind this synergistic effect, which was inhibited by the addition of the mevalonate pathway products, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Furthermore, we aimed to determine the effect of ZOL and FLU combination on RhoA and Ras guanosine 5′-triphosphate (GTP)-proteins. The combination induced a marked accumulation in RhoA and unprenylated Ras. GGPP and FPP reversed the increase in the amount of both proteins. These results indicated that the combination treatment impaired RhoA and Ras signaling pathway by the inhibition of geranylgeranylation and/or farnesylation. This study provides a potentially effective approach for the treatment of pancreatic cancer using a combination treatment of ZOL and FLU.

著者

Takeshi Sase Yasuo Kuwasawa Takashi Ogino

出版者

Japan Council for Renewable Energy

雑誌

グランド再生可能エネルギー国際会議論文集 (ISSN:24340871)

巻号頁・発行日

pp.90, 2018 (Released:2019-03-07)

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Storage battery is utilized in the grid, in the household, combined with solar power generation, fuel cell, for accumulating overpowered electricity and emitting it while it runs short. But we have very little information of energy loss with storage battery, during accumulating and emitting electricity, by transferring direct current to alternating one and reverse process. The authors have evaluated saving energy and energy loss of fuel cell and storage battery combined system. It says that not only fuel cell trait, whose efficiency is high at full load, but also storage battery trait, which loses some electricity during accumulating, emitting and transferring, should be evaluated. In addition to that, we have tried to evaluate saving energy and energy loss of solar power generation and storage battery combined system. We have got lots of information on these issues.