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Enantiospecific Synthesis and Cytotoxicity Evaluation of Oximidine II Analogues
Author(s) -
Schneider Christopher M.,
Li Wei,
Khownium Kriangsak,
Lushington Gerald H.,
Georg Gunda I.
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600024
Subject(s) - cytotoxicity , stereochemistry , side chain , amide , chemistry , natural product , allylic rearrangement , sulfone , cancer cell lines , combinatorial chemistry , biochemistry , organic chemistry , cancer cell , cancer , in vitro , biology , catalysis , polymer , genetics
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.