Synthesis and anticancer profile of novel FTY720 analogues with azobenzene frameworks

A short synthetic route towards novel cytotoxic FTY720 analogues bearing a variously substituted azo-benzene 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 ac-tivity 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 isomer-isation and thermal relaxation rate were determined.(c) 2023 Elsevier Ltd. All rights reserved.

Automated summary

A short synthetic route towards novel cytotoxic FTY720 analogues with variously substituted azo-benzene units was developed. The target compounds were constructed using Wittig olefination or Mills reaction as key processes. Preliminary biological screening showed promising antiproliferative activity of the newly synthesised derivatives against Jurkat, HeLa, and HCT-116 cells, comparable or higher than cisplatin. The structure-activity relationship indicated that the loss of the alkyl side chain or its substitution with a hydroxymethyl group on the azobenzene core seemed to be detrimental for the resulting cytotoxic profile. To probe the photochromic properties, the reversible E/Z isomerization and thermal relaxation rate of the final derivatives were determined.