Kenji Tokuhisa
Tosoh
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Publication
Featured researches published by Kenji Tokuhisa.
Bioorganic & Medicinal Chemistry Letters | 1997
Hiromitsu Takayama; Yasuo Iimura; Mariko Kitajima; Norio Aimi; Kenji Konno; Hiroshi Inoue; Masatoshi Fujiwara; Tadashi Mizuta; Tomoyuki Yokota; Shiro Shigeta; Kenji Tokuhisa; Yasuaki Hanasaki; Kimio Katsuura
Abstract An indole alkaloid, hirsutine (1), was found to exhibit potent inhibitory effect against influenza A virus in vitro, and the essential structural feature for revealing the activity was elucidated by study of the structure-activity relationship using natural and synthetic derivatives of 1.
Archives of Virology | 1998
Masatoshi Fujiwara; Mika Okamoto; K. Ijichi; Kenji Tokuhisa; Yasuaki Hanasaki; Kimio Katsuura; Daisuke Uemura; Shiro Shigeta; Kenji Konno; Tomoyuki Yokota; Masanori Baba
SummaryWe have previously reported that ingenol derivatives are highly potent inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in acutely infected cells. In this study, however, we have found that some ingenol derivatives strongly enhance the replication of HIV-1 in chronically infected cells at nanomolar concentrations. One of the derivatives could activate nuclear factor κB(NF-κB), a potent inducer of HIV-1 replication, through the activation of protein kinase C (PKC). Whereas another derivative, which affected neither PKC nor NF-κB, significantly enhanced HIV-1 replication, suggesting that a PKC-independent mechanism may also exist in ingenol derivative-induced HIV-1 upregulation.
Antiviral Chemistry & Chemotherapy | 1996
Masatoshi Fujiwara; K. Ijichi; Kenji Tokuhisa; Kimio Katsuura; Gui-Yang-Sheng Wang; Daisuke Uemura; Shiro Shigeta; Kenji Konno; Tomoyuki Yokota; Masanori Baba
Ingenol 3,5,20-triacetate has recently been identified as a highly potent and selective inhibitor of HIV replication in vitro. To evaluate the potential of ingenol derivatives as anti-HIV agents, several ingenol derivatives have been synthesized and investigated for their anti-HIV activities, structure-activity relationships, and possible mechanisms of action. Among the ingenol derivatives, 13-hydroxyingenol-3-(2,3-dimethylbutanoate)-13-dodecanoate (RD4-2138) proved to be a highly potent and selective inhibitor of HIV replication. Its 50% effective concentration for viral replication in MT-4 cells was 0.07-0.5 nM depending on viral strains, including HIV-2. This concentration was approximately 105-fold lower than its cytotoxic threshold. RD4-2138 was also inhibitory to the syncytium formation induced by cocultivation of Molt-4 cells with Molt-4/IIIB cells (Molt-4 cells chronically infected with HIV-1). Some correlation was observed with the ingenol derivatives between their inhibitory effects on HTLV-IIIB replication and surface CD4 expression in MT-4 cells, suggesting that the mechanism of inhibition is in part attributed to the inhibition of virus adsorption through down-regulation of CD4 molecules in the host cells. However, such correlation was not identified between the inhibition of HTLV-IIIB and the activation of protein kinase C. Thus, they might have a potential as effective anti-HIV agents when toxicity in vivo could be elucidated.
Biotechnology Letters | 2001
Satoshi Hanzawa; Seigo Oe; Kenji Tokuhisa; Kazuhisa Kawano; Tetsuo Kobayashi; Toshiaki Kudo; Hitoshi Kakidani
Hyper-thermostable aminotransferase from Thermococcus profundus (MsAT) was used to synthesize 3-(2-naphthyl)-l-alanine (Nal) by transamination between its corresponding α-keto acid, 3-(2-naphthyl)pyruvate (NPA) and l-glutamate (Glu) at 70 °C. Equilibrium of this reaction was shifted toward Nal production due to its low solubility, giving rise to Nal precipitate. Optically pure Nal (>99% ee) was synthesized with 93% (mol mol−1) yield from 180 mM NPA and 360 mM Glu.
Antiviral Chemistry & Chemotherapy | 1999
Masatoshi Fujiwara; Eiichi Kodama; Masayuki Okamoto; Kenji Tokuhisa; Teruhiko Ide; Yasuaki Hanasaki; Kimio Katsuura; Hiromitsu Takayama; Norio Aimi; Hiroaki Mitsuya; Shiro Shigeta; Kenji Konno; Tomoyuki Yokota; Masanori Baba
The non-nucleoside reverse transcriptase (RT) inhibitor RD4–2217 is a thiadiazole derivative that has proved to be a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in vitro. In this study we examined genotypic and phenotypic characteristics of RD4–2217-resistant mutants that have been obtained by serial passage of HIV-1 in MT-4 cells in the presence of increasing concentrations (0.05, 0.25, 1 and 10 μM) of the compound. The strains obtained, IIIB/2217RE/0.05 and IIIB/2217RE/0.25, were two-and 15-fold resistant to RD4–2217, respectively, whereas IIIB/2217RE/1 and IIIB/2217RE/10 displayed 161-and >238-fold resistance, respectively. Both IIIB/2217RE/1 and IIIB/2217RE/10 had two amino acid substitutions, V189I and T240I, in the RT. Furthermore, RD4–2217 did not inhibit the replication of an HIV-1 molecular clone, which had the same mutation, at concentrations up to 10 μM, indicating that the V189I plus T240I mutation confers high-level resistance to RD4–2217. Interestingly, the replicability of IIIB/2217RE/1 and IIIB/2217RE/10 appeared to be lower than that of wild-type IIIB in MT-4 cells, suggesting that the V189I plus T240I mutation may impair the enzymatic activity of HIV-1 RT.
Journal of Fluorine Chemistry | 2010
Tatsuhito Kino; Yu Nagase; Yuhki Ohtsuka; Kyoko Yamamoto; Daisuke Uraguchi; Kenji Tokuhisa; Tetsu Yamakawa
Antimicrobial Agents and Chemotherapy | 1996
Masatoshi Fujiwara; K. Ijichi; Kenji Tokuhisa; Kimio Katsuura; Shiro Shigeta; Kenji Konno; Gui-Yang-Sheng Wang; Daisuke Uemura; Tomoyuki Yokota; Masanori Baba
Archive | 2006
Satoru Miyazawa; Kazuhiko Maeda; Kenji Tokuhisa; Shoji Arai
Applied Catalysis A-general | 2008
Daisuke Uraguchi; Kyoko Yamamoto; Yuhki Ohtsuka; Kenji Tokuhisa; Tetsu Yamakawa
Tetrahedron | 2012
Yuhki Ohtsuka; Daisuke Uraguchi; Kyoko Yamamoto; Kenji Tokuhisa; Tetsu Yamakawa