2019年度大阪薬科大学 教育・研究振興基金 優秀論文賞の受賞者が決定

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2020.05.12
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2019年度大阪薬科大学 教育・研究振興基金 優秀論文賞の受賞者が決定

 大阪薬科大学 教育・研究振興基金優秀論文賞は、若手専任教員が本学で行った研究成果の中で、特に優れた研究論文を発表した者を顕彰し、更なる研究活動の発展を支援することを目的としたものです。
 2019年度は下記の3名が受賞となりました。
助成対象者 菊地 崇 助教(医薬分子化学研究室)
論 文 名 Strophasterols E and F: Rearranged ergostane-type sterols from Pleurotus eryngii
掲 載 雑 誌 Bioorganic Chemistry, 89, 103011 (2019)
概   要 Strophasterol E (1) and strophasterol F (2) were isolated from the fruiting bodies of Pleurotus eryngii, together with four new ergostane-type sterols (3–6). Single-crystal X-ray diffraction analysis performed on the tris-p-bromobenzoate derivatives of compounds 1 and 2 allowed these two compounds to be identified as the structurally rare (22S,23R)- and (22S,23S)-5α,6α-epoxy-3β,7β,23-trihydroxy-15(14→22)-abeo-ergost-8-en-14-one, respectively. The inhibitory effects of compounds 1–6, and of a positive control, L-NMMA, on NO production were examined on lipopolysaccharide-stimulated mouse macrophage (RAW264.7) cells. Compounds 1–6 did not exhibit cytotoxicity in the 1–30 μM concentration range on RAW 264.7 cells. Compound 5 exhibited a superior inhibitory effect on NO production with respect to L-NMMA.
助成対象者 小池敦資 助教(病態生化学研究室)
論 文 名 Pan-caspase inhibitors induce necroptosis via ROS-mediated activation of mixed lineage kinase domain-like protein and p38 in classically activated macrophages
掲 載 雑 誌 Experimental Cell Research.380 (2),171-179 (2019)
概   要 Classically activated macrophages (CAMs) play a crucial protective role in the host by killing the invading pathogens. However, excessive activation of CAMs causes chronic inflammation leading to host tissue damage. Thus, control of macrophage activity is necessary to prevent chronic inflammation. To date, regulation of CAMs in the development of chronic inflammatory diseases has not been elucidated. In this study, we investigated the effect of a pan-caspase inhibitor, zVAD-fmk, in cell death in lipopolysaccharide (LPS)-activated macrophages, CAMs. Necrostatin-1, an inhibitor of necroptosis, inhibited zVAD-fmk-induced cell death in CAMs. The expression of mixed lineage kinase domain-like protein (MLKL) involved in the necroptosis pathway was up-regulated by LPS in CAMs. zVAD-fmk enhanced the phosphorylation of MLKL in CAMs. Moreover, inhibition of activation of mitogen activated protein kinase p38 and generation of reactive oxygen species (ROS) reduced zVAD-fmk-induced cell death in CAMs. Inhibition of ROS generation decreased the activation of MLKL and p38 in zVAD-fmk-treated CAMs. These results, taken together, indicate that zVAD-fmk-induced cell death occurred by necroptosis through ROS-mediated activation of MLKL and p38 in CAMs. Elucidation of the molecular mechanism underlying zVAD-fmk-induced necroptosis in CAMs might help in better understanding its significance in chronic inflammatory diseases.
助成対象者 米山弘樹 助教(有機薬化学研究室)
論 文 名 Efficient Synthesis of a 5 -Reductase Inhibitor, 3-(Tetrazol-5-yl)-3,5-pregnadien-20-one through Allylic Rearrangement of Cyanophosphates
掲 載 雑 誌 Synthesis.51,1791-1794 (2019)
概   要  黄体ホルモンであるプロゲステロンを原料に、強力な5α-レダクターゼ阻害剤(IC50:15.6 nM)を持ち、前立腺がんや前立腺肥大症の治療薬に期待される3-(テトラゾール-5-イル)-3,5-プレグナジエン-20-オン(TzPD)の効率的で実用的な合成法の開発に成功した。
ケトンより容易に合成できるシアノホスフェート(CP)のアリル転位を鍵反応とし、また同時に保護基として使用することにより、4工程、総収率92%でTzPDの合成を達成した。本合成方法を用いることにより、様々なステロイド型5AR阻害剤の合成を容易に行うことが出来るようになった。
 さらに、本研究によりCPの応用範囲が広がったため、現在、多くの生物活性物質の合成へと応用展開している。

We have described the efficient and practical synthesis of 3-(tetrazol-5-yl)-3,5-pregnadien-20-one (TzPD), which is a potent 5α-reductase inhibitor (IC50: 15.6 nM), from progesterone in 92% overall yield in four steps by using an allylic rearrangement in cyanophosphates (CPs). The present method for the synthesis of TzPD is experimentally straightforward and it is suitable for the synthesis of some steroidal 5AR inhibitors. The present study also helps increase the diversity of available CPs. In addition, application of this method involving CPs to the synthesis of many biologically important substrates is under investigation in our laboratory.
※記載は、五十音順

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