Enantiospecific Synthesis and Cytotoxicity Evaluation of Oximidine II Analogues |
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| Authors: | Dr Christopher M Schneider Dr Wei Li Dr Kriangsak Khownium Dr Gerald H Lushington Prof?Dr Gunda I Georg |
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| Affiliation: | 1. Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, USA;2. Department of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, University of Minnesota, Minneapolis, MN, USA;3. Molecular Graphics & Modeling Laboratory, University of Kansas, Lawrence, KS, USA |
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| 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. |
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| Keywords: | antitumor agents benzolactone enamides cytotoxicity natural products oximidines |
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