A series of platinum compounds 2a-5a and 2b-5b with fluoro-functional groups are designed and synthesized. Among them, complex 2b is the most effective agent with 3-hydroxy-3-(trifluoromethyl)cyclobutane-1,1-dicarboxylate as a leaving ligand, which showed better cytotoxic activity than compounds containing only CF₃ or OH group at 3-position of cyclobutane-1,1-dicarboxylate. The water solubility of 2a is better than that of carboplatin (32 mg/mL vs. 16 mg/mL), and its antitumor activity on A549 is 4.6-fold higher than that of carboplatin. The IC₅₀ value of 2b on A549 cells is 4.73 ± 0.64 μM, which is comparable to that of oxaliplatin and higher than that of carboplatin. Meanwhile, 2a and 2b are less toxic than oxaliplatin and cisplatin toward BEAS-2B cells. Moreover, 2a and 2b induce cell apoptosis in vitro by the Bax-Bcl-2-caspase-3 pathway and ferroptosis through inhibiting GPx-4 and elevating COX2. Results from in vivo experiment show that the inhibition rate of A549 xenograft tumor is cisplatin > 2b > oxaliplatin > 2a > carboplatin.

设计合成了一系列具有氟官能团的铂化合物2a - 5a和2b-5b 。其中，络合物2b是最有效的试剂，以3-羟基-3-(三氟甲基)环丁烷-1,1-二羧酸盐作为离去配体，与仅在3位仅含有CF ₃或OH基团的化合物相比，其具有更好的细胞毒活性。环丁烷-1,1-二羧酸盐。2a的水溶性优于卡铂（32 mg/mL vs. 16 mg/mL），对A549的抗肿瘤活性比卡铂高4.6倍。IC ₅₀值2b在 A549 细胞上为 4.73 ± 0.64 μM，与奥沙利铂相当，高于卡铂。同时，2a和2b对 BEAS-2B 细胞的毒性低于奥沙利铂和顺铂。此外，2a和2b在体外通过 Bax-Bcl-2-caspase-3 途径诱导细胞凋亡，并通过抑制 GPx-4 和升高 COX2 诱导细胞铁死亡。体内实验结果表明，A549异种移植瘤的抑制率顺铂> 2b  >奥沙利铂> 2a  >卡铂。