Synthesis and biological evaluation of l-cysteine derivatives as mitotic kinesin Eg5 inhibitors

Inhibition of Eg5 represents a novel approach for the treatment of cancer. Here, we report the synthesis and structure-activity relationship of S-trityl-l-cysteine (STLC) derivatives as Eg5 inhibitors. Some of these derivatives such as 4f demonstrated enhanced inhibitory activity against Eg5 and induced mitotic arrest with characteristic monoastral spindles in HeLa cells.

Graphical abstractThe synthesis and evaluation for Eg5 inhibitory activity of S-substituted-l-cysteine derivatives are reported. Derivative 4f (R1 = H, R2 = OH, R3 = 4-OMe) demonstrated potent and selective inhibitory activity against Eg5 and induced mitotic arrest with characteristic monoastral spindles in HeLa cells.Figure optionsDownload full-size imageDownload as PowerPoint slide