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 Q.
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.
- Journal
- European Journal of Medicinal Chemistry
- Volume
- 144
- Year
- 2018
- Start Page
- 751-757
- URL
- https://dx.doi.org/10.1016/j.ejmech.2017.11.022
- ISBN/ISSN
- 1768-3254; 0223-5234
- DOI
- 10.1016/j.ejmech.2017.11.022