Cytoprotective agents are mainly used to protect the gastrointestinal tract linings and in the treatment of gastric ulcers. These agents are devoid of appreciable cytotoxic or cytostatic effects, and medicinal chemistry efforts to modify them into anticancer agents are rare. A drug repurposing campaign initiated in our laboratory with the primary focus of discovering brain cancer drugs resulted in drug-dye conjugate 1, a combination of the cytoprotective agent troxipide and heptamethine cyanine dye MHI 148. The drug-dye conjugate 1 was evaluated in three different patient-derived adult glioblastoma cell lines, commercially available U87 glioblastoma, and one paediatric glioblastoma cell line. In all cases, the conjugate 1 showed potent cytotoxic activity with nanomolar potency (EC₅₀: 267 nM). Interestingly, troxipide alone does not show any cytotoxic and cytostatic activity in the above cell lines. We also observe a synergistic effect of 1 with temozolomide (TMZ), the standard drug used for glioblastoma treatment, even though the cell lines we used in this study were resistant to TMZ treatment. Herein we disclose the synthesis and in vitro activity of drug-dye conjugate 1 for treatment of difficult-to-treat brain cancers such as glioblastoma.

细胞保护剂主要用于保护胃肠道内壁和治疗胃溃疡。这些药剂没有明显的细胞毒性或细胞抑制作用，将它们改造成抗癌剂的药物化学努力很少见。在我们的实验室发起了一项药物再利用活动，主要重点是发现脑癌药物，从而产生了药物-染料偶联物1，它是细胞保护剂曲昔派和七甲基菁染料 MHI 148 的组合。药物-染料偶联物1在三种不同的情况下进行了评估患者来源的成人胶质母细胞瘤细胞系、市售的 U87 胶质母细胞瘤细胞系和一种儿科胶质母细胞瘤细胞系。在所有情况下，共轭1显示出具有纳摩尔效力（EC ₅₀：267 nM）的有效细胞毒活性。有趣的是，单独的troxipide 在上述细胞系中不显示任何细胞毒性和细胞抑制活性。我们还观察到1与用于胶质母细胞瘤治疗的标准药物替莫唑胺 (TMZ)的协同作用，尽管我们在本研究中使用的细胞系对 TMZ 治疗具有抗性。在此，我们公开了用于治疗难以治疗的脑癌（如胶质母细胞瘤）的药物-染料偶联物1的合成和体外活性。