Light-Controlled\nAnticancer Activity and Cellular\nUptake of a Photoswitchable Cisplatin Analogue

A photoactive analogue of cisplatin was synthesized with\ntwo arylazopyrazole\nligands, able to undergo <i>trans</i>–<i>cis</i>/<i>cis</i>–<i>trans</i> photoisomerizations.\nThe <i>cis</i> photoisomer showed a dark half-life of 9\ndays. The cytotoxicities of both photoisomers of the complex were\ndetermined in several cancer and normal cell lines and compared to\nthat of cisplatin. The <i>trans</i> photoisomer of the complex\nwas much more cytotoxic than both the <i>cis</i> photoisomer\nand cisplatin, and was more toxic for cancer (4T1) than for normal\n(NMuMG) murine breast cells. 4T1 cell death occurred through necrosis.\nPhotoisomerization of the <i>trans</i> and <i>cis</i> photoisomers internalized by the 4T1 cells increased and decreased\ntheir viability, respectively. The cellular uptake of the <i>trans</i> photoisomer was stronger than that of both the <i>cis</i> photoisomer and cisplatin. Both photoisomers interacted\nwith DNA faster than cisplatin. The <i>trans</i> photoisomer\nwas bound stronger by bovine serum albumin and induced a greater decrease\nin cellular glutathione levels than the <i>cis</i> photoisomer.