Synthesis and anticancer profile of novel FTY720 analogues with azobenzene frameworks

Abstract

A short synthetic route towards novel cytotoxic FTY720 analogues bearing a variously substituted azobenzene unit was developed. The target compounds were constructed either via a Wittig olefination or Mills reaction as the key processes. Preliminary biological screening revealed the antiproliferative activity of several newly synthesised derivatives against Jurkat, HeLa and HCT-116 cells to be quite promising, comparable or higher than the potency of cisplatin (Brinkmann et al., 2010) [1]. The structure-activity relationship showed that a loss of the alkyl side chain on the azobenzene core or its substitution with hydroxymethyl moiety seem to be detrimental for the resulting cytotoxic profile in this series of derivatives. To probe the photochromic properties of the final derivatives, the reversible E/Z isomerisation and thermal relaxation rate were determined.