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Skeletal Optimization of Cytotoxic Lipidic Dialkynylcarbinols
Author(s) -
Bourkhis Maroua,
Gaspard Hafida,
Rullière Pauline,
de Almeida Diana K. C.,
Listunov Dymytrii,
Joly Etienne,
Abderrahim Raoudha,
de Mattos Marcos C.,
de Oliveira Maria C. F.,
Maraval Valérie,
Chauvin Remi,
Génisson Yves
Publication year - 2018
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.201800118
Subject(s) - kinetic resolution , enantiomer , cytotoxicity , chemistry , stereochemistry , carbon skeleton , combinatorial chemistry , cytotoxic t cell , cancer cell lines , enzyme , cancer cell , enantioselective synthesis , organic chemistry , biochemistry , in vitro , cancer , biology , catalysis , genetics
In line with a recent study of the pharmacological potential of bioinspired synthetic acetylenic lipids, after identification of the terminal dialkynylcarbinol (DAC) and butadiynyl alkynylcarbinol (BAC) moieties as functional antitumor pharmacophoric units, this work specifically addresses the issue of carbon backbone length. A systematic variation of the aliphatic chain length was thus carried out in both the DAC and BAC series. The critical impact of the length of the lipidic skeleton was first confirmed in the racemic series, with the highest cytotoxic activity observed for C 17 to C 18 backbones. Enantiomerically enriched samples were prepared by asymmetric synthesis of the optimal C 18 DAC and C 17 BAC derivatives. Samples with upgraded enantiomeric purity were alternatively produced by enzymatic kinetic resolution. Eutomers possessing the S configuration displayed cytotoxicity IC 50 values as low as 15 n m against HCT116 cancer cells, the highest level of activity reached to date in this series.