New insights into structure-activity relationship of ipomoeassin F from its bioisosteric 5-oxa/aza analogues

作者：Zong Guanghui; Sun Xianwei; Bhakta Rima; Whisenhunt Lucas; Hu Zhijian; Wang Feng; Shi Wei Q^*

来源：European Journal of Medicinal Chemistry, 2018, 144: 751-757.

DOI：10.1016/j.ejmech.2017.11.022

• Resin glycosides
• Ipomoeassin F
• Bioisosteric ester/amide analogues
• Macrolide
• Cytotoxicity

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-CH2 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.

• 出版日期2018-1-20