Synthesis and biological activity of sphingosines with integrated azobenzene switches

Abstract

A flexible synthetic approach towards biologically active sphingoid base-like compounds with an integrated azobenzene framework was achieved via installing a chiral amino-alcohol fragment into the azobenzene system by utilizing the Wittig olefination of substituted (E)-triphenyl[4-(phenyldiazenyl)benzyl]phosphonium salts and D-isoascorbic acid derived aldehydes. All the prepared derivatives underwent a series of experiments to probe their photochromic properties, including the reversible E/Z isomerisation, material fatigue and thermal relaxation rate. The targeted E- and Z-isomeric sphingoid analogues were screened in vitro for anticancer activity on a panel of seven human malignant cell lines. Cell viability experiments revealed outstanding antiproliferative/cytotoxic activities of all the tested compounds with IC₅₀ values in the low micromolar range for the most active derivatives. The biological activity of E- and Z-isomeric forms is different. Their entirely accurate differentiation is prevented by the rapid thermal relaxation of the corresponding Z-isomers.