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

by Zong, Guanghui; Sun, Xianwei; Bhakta, Rima; Whisenhunt, Lucas; Hu, Zhijian; Wang, Feng; Shi, Wei

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. (C) 2017 Elsevier Masson SAS. All rights reserved.

Journal
European journal of Medicinal Chemistry
Volume
144
Year
2018
Start Page
751
ISBN/ISSN
1768-3254; 0223-5234
DOI
10.1016/j.ejmech.2017.11.022