来自其生物电子等排体5-氧杂/氮杂类似物的番薯素F构效关系的新见解。
New insights into structure-activity relationship of ipomoeassin F from its bioisosteric 5-oxa/aza analogues.
作者信息
Zong Guanghui, Sun Xianwei, Bhakta Rima, Whisenhunt Lucas, Hu Zhijian, Wang Feng, Shi Wei Q
机构信息
Department of Chemistry and Biochemistry, J. William Fulbright College of Arts & Science, University of Arkansas, Fayetteville, AR, 72701, USA.
Department of Chemistry and Biochemistry, J. William Fulbright College of Arts & Science, University of Arkansas, Fayetteville, AR, 72701, USA.
出版信息
Eur J Med Chem. 2018 Jan 20;144:751-757. doi: 10.1016/j.ejmech.2017.11.022. Epub 2017 Dec 12.
Ipomoeassin F, a plant-derived macrolide, exhibited single-digit nanomolar growth inhibition activity against many cancer cell lines. In this report, a series of 5-oxa/aza analogues was prepared and screened for cytotoxicity. Replacement of 5-CH with O/NH simplified the synthesis and led to only a small activity loss. N-methylation almost completely restored the potency. Further studies with additional 5-oxa analogues suggested, for the first time, that size and flexibility of the ring also significantly influence the bioactivity of ipomoeassin F.
番薯素F是一种植物来源的大环内酯，对多种癌细胞系表现出个位数纳摩尔级别的生长抑制活性。在本报告中，制备了一系列5-氧杂/氮杂类似物并筛选其细胞毒性。用氧/氮取代5-碳氢简化了合成过程，且仅导致活性有小幅损失。N-甲基化几乎完全恢复了活性。对更多5-氧杂类似物的进一步研究首次表明，环的大小和柔韧性也对番薯素F的生物活性有显著影响。
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