Light-Controlled Anticancer Activity and Cellular Uptake of a Photoswitchable Cisplatin Analogue

A photoactive analogue of cisplatin was synthesized with two arylazopyrazole ligands, able to undergo <i>trans</i>-<i>cis</i>/<i>cis</i>-<i>trans</i> photoisomerizations. The <i>cis</i> photoisomer showed a dark half-life of 9 days. The cytotoxicities of both photoisomers of the complex were determined in several cancer and normal cell lines and compared to that of cisplatin. The <i>trans</i> photoisomer of the complex was much more cytotoxic than both the <i>cis</i> photoisomer and cisplatin, and was more toxic for cancer (4T1) than for normal (NMuMG) murine breast cells. 4T1 cell death occurred through necrosis. Photoisomerization of the <i>trans</i> and <i>cis</i> photoisomers internalized by the 4T1 cells increased and decreased their 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 with DNA faster than cisplatin. The <i>trans</i> photoisomer was bound stronger by bovine serum albumin and induced a greater decrease in cellular glutathione levels than the <i>cis</i> photoisomer.