Enantiospecific Synthesis and Cytotoxicity Evaluation of Oximidine II Analogues

Christopher M. Schneider, Wei Li, Kriangsak Khownium, Gerald H. Lushington, Gunda I. Georg

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Analogues of the anticancer natural product oximidine II were prepared and evaluated for cytotoxicity. One analogue of oximidine II that carries a C15 allylic amide side chain as well as two analogues with C15 vinyl sulfone side chains were found to lack cytotoxicity against the cancer cell line SK-Mel-5, thereby confirming the necessity of the C15 enamide side chain of oximidine II for cytotoxicity. Four analogues, designed by comparative molecular similarity index analysis (CoMSIA), that feature a less complex macrolactone scaffold were prepared and tested. The two analogues carrying a C15 vinyl sulfone group and the two analogues with a C15 oximidine II enamide side chain showed weak cytotoxicity against the SK-Mel-5 cell line and other cell lines, indicating that the designed simplified macrocycles cannot replace the oximidine II macrocycle.

Original languageEnglish (US)
Pages (from-to)1600-1616
Number of pages17
JournalChemMedChem
DOIs
StatePublished - 2016

Bibliographical note

Funding Information:
These studies were supported by the University of Minnesota through the Vince and McKnight Endowed Chairs. C.M.S. acknowledges a pre-doctoral fellowship from the US National Institutes of Health (NIH) (NIH T32 GM 008545) while at the University of Kansas. K.K. thanks the Royal Thai Government for fellowship support. The cytotoxicity assays were performed by Defeng Tian in the Institute for Therapeutics Discovery and Development at the University of Minnesota. Special acknowledgements to Rebecca A. Cuellar and Sara Coulup for their help in preparing the spectra, and Dr. Subhashree Francis for LC?MS analyses.

Publisher Copyright:
© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

Keywords

  • antitumor agents
  • benzolactone enamides
  • cytotoxicity
  • natural products
  • oximidines

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