Improvement of both plasmepsin inhibitory activity and antimalarial activity by 2-aminoethylamino substitution
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- 作者：Takuya Miura ; Koushi Hidaka ; Tsuyoshi Uemura ; Keisuke Kashimoto ; Yuto Hori ; Yuko Kawasaki ; Adam J. Ruben ; Ernesto Freire ; Tooru Kimura ; Yoshiaki Kiso
- 关键词：Antimalarial drug ; Aspartic protease ; Plasmepsin inhibitor ; Hydoxymethylcarbonyl ; Allophenylnorstatine ; Peptidomimetics
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2010
- 出版时间：15 August 2010
- 年：2010
- 卷：20
- 期：16
- 页码：4836-4839
- 全文大小：578 K
文摘
We attached 2-aminoethylamino groups to allophenylnorstatine-containing plasmepsin (Plm) inhibitors and investigated SAR of the methyl or ethyl substitutions on the amino groups. Unexpectedly, compounds 22 (KNI-10743) and 25 (KNI-10742) exhibited extremely potent Plm II inhibitory activities (Ki <0.1 nM). Moreover, among our peptidomimetic Plm inhibitors, we identified the compounds with the highest antimalarial activity using a SYBR Green I-based fluorescence assay.