Structure-cytotoxic activity relationship of sesquilignan, morinol A

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• 作者：Satoshi Yamauchi ; Saya Kawahara ; Tuti Wukirsari ; Hisashi Nishiwaki ; Kosuke Nishi ; Takuya Sugahara ; Koichi Akiyama ; Taro Kishida
• 关键词：Lignan ; Sesquilignan ; Cytotoxic activity ; Morinol
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：1 September, 2013
• 年：2013
• 卷：23
• 期：17
• 页码：4923-4930
• 全文大小：3970 K

文摘

The cytotoxic activities of sesquilignans, (7S,8S,7¡äR,8¡äR)- and (7R,8R,7¡äS,8¡äS)-morinol A and (7S,8S,7¡äS,8¡äS)- and (7R,8R,7¡äR,8¡äR)-morinol B were compared, showing no significant difference between stereoisomers (IC₅₀ = 24-35 ¦ÌM). As a next stage, the effect of substituents at 7, 7¡ä, and 7¡å-aromatic ring on the activity was evaluated to find out the higher activity of (7S,8S,7¡äR,8¡äR)-7,7¡ä,7¡å-phenyl derivative 18 (IC₅₀ = 6-7 ¦ÌM). In the research on the structure-activity relationship of 7¡å-position of (7S,8S,7¡äR,8¡äR)-7,7¡ä,7¡å-phenyl derivative 18, the most potent compounds were 7,7¡ä,7¡å-phenyl derivative 18 (IC₅₀ = 6 ¦ÌM) against HeLa cells. Against HL-60 cells, 7¡å-(4-nitrophenyl)-7,7¡ä-phenyl derivative 33 and 7¡å-hexyl-7,7¡ä-phenyl derivative 37 (IC₅₀ = 5 ¦ÌM) showed highest activity. We discovered the compounds showed four to sevenfold potent activity than that of natural (7S,8S,7¡äR,8¡äR)-morinol A. It was also confirmed that the 7¡ä-benzylic hydroxy group have an important role for exhibiting activity, on the other hand, the resonance system of cinnamyl structure is not crucial for the potent activity.