Optically active iodohelicene derivatives exhibit histamine N-methyl transferase inhibitory activity
Optically active iodohelicene derivatives exhibit histamine N-methyl transferase inhibitory activity
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DOI：
10.1038/s41429-018-0118-z
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发表时间：
2018-10
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影响因子：
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通讯作者：
W. Ichinose;Tsukasa Sawato;Haruna Kitano;Yasuhiro Shinozaki;M. Arisawa;Nozomi Saito;T. Yoshikawa
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文献类型：
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作者：
W. Ichinose;Tsukasa Sawato;Haruna Kitano;Yasuhiro Shinozaki;M. Arisawa;Nozomi Saito;T. Yoshikawa
旋光性螺旋烯衍生物抑制组胺-甲基转移酶（HNMT）的活性。具体来说，具有6-碘和5-三氟甲烷磺酰氧基的甲基(P)-1,12-二甲基苯并[c]菲-8-羧酸酯对HNMT活性的抑制作用在IC50 μM量级。手性很重要，(M)-异构体的活性大大降低。6-碘基团也是必不可少的，这表明卤素键参与蛋白质结合。磺酸基上的取代基也会影响抑制活性。
Optically active helicene derivatives inhibit the activity on histamineN-methyl transferase (HNMT). Specifically, methyl (P)-1,12-dimethylbenzo[c]phenanthrene-8-carboxylate with 6-iodo and 5-trifluoromethanesulfonyloxy groups inhibits HNMT activity on the μM order of IC50. Chirality is important, and (M)-isomers exhibits substantially reduced activity. The 6-iodo group is also essential, which suggests the involvement of halogen bonds in protein binding. Substituents on the sulfonate moiety also affect the inhibitory activity.