Development of photochromic anti-cancer agent : kinesin Eg5 inhibitor

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The mitotic kinesin Eg5 is essential for the formation of bipolar spindles during eukaryotic cell division, it has been considered as a potential target for cancer treatment. STLC is one of the inhibitors of Eg5 whose molecular mechanism of inhibition was well studied. In this study, we synthesized a novel photochromic STLC analogues, ACTAB, composed of a trityl group, azobenzene, and Acetyl-L-cysteine, which exhibits cis-trans photoisomerization in order to photocontrol the function of Eg5. ACTAB exhibited cis-trans photoisomerization upon alternating irradiation at two different visible wavelengths. ACTAB induced reversible changes in the inhibitory activity of ATPase and motor activities correlating with the cis-trans photoisomerization. Compared to cis-ACTAB, trans-ACTAB reduced ATPase activity and microtubule gliding velocity more significantly. These results suggest that ACTAB could be used as photochromic inhibitor of Eg5 to achieve photocontrol of living cells.