Premium
Cover Picture: Enantiospecific Synthesis and Cytotoxicity Evaluation of Oximidine II Analogues (ChemMedChem 15/2016)
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 - Reports
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600376
Subject(s) - moiety , amide , allylic rearrangement , cytotoxicity , chemistry , stereochemistry , electrophile , sulfone , combinatorial chemistry , natural product , front cover , cover (algebra) , organic chemistry , biochemistry , in vitro , mechanical engineering , engineering , catalysis
The front cover picture shows V‐ATPase (vacuolar‐type H + ‐ATPase), its inhibitor oximidine II (center), and analogues of the inhibitor, which were synthesized to probe the hypothesis that the enamide functionality of the parent compound could be replaced with physiologically stable functional groups bearing an allylic amide or an electrophilic vinyl sulfone functionality, and that the analogues would retain bioactivity. The allylic amide and sulfone side chain analogues lacked cytotoxicity, adding further evidence that an enamide moiety is required for the biological activity of the benzolactone enamide family of natural products. Analogues that were designed and synthesized following computational studies fit well into the V‐ATPase binding pocket but showed weak cytotoxic activities, demonstrating that this simplified scaffold cannot replace the macrocycle of the natural products. More information can be found in the Full Paper by Gunda I. Georg, et al. on page 1600 in Issue 15, 2016 (DOI: 10.1002/cmdc.201600024).