2. Academic Validation
  3. New insights into structure-activity relationship of ipomoeassin F from its bioisosteric 5-oxa/aza analogues

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

  • Eur J Med Chem. 2018 Jan 20:144:751-757. doi: 10.1016/j.ejmech.2017.11.022.
Guanghui Zong 1,  Xianwei Sun 1,  Rima Bhakta 1,  Lucas Whisenhunt 1,  Zhijian Hu 1,  Feng Wang 1,  Wei Q Shi 2
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, J. William Fulbright College of Arts & Science, University of Arkansas, Fayetteville, AR, 72701, USA.
  • 2 Department of Chemistry and Biochemistry, J. William Fulbright College of Arts & Science, University of Arkansas, Fayetteville, AR, 72701, USA. Electronic address: weishi@uark.edu.
PMID: 29291442 DOI: 10.1016/j.ejmech.2017.11.022
Abstract

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.

Keywords

Bioisosteric ester/amide analogues; Cytotoxicity; Ipomoeassin F; Macrolide; Resin glycosides.

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