Abstract Four new benzopyran- platinum (Pt) complexes, [Pt(C1)Cl2]⋅CH3OH (C1-Pt), [Pt(C2)Cl2] (C2-Pt), [Pt(C3)Cl2] (C3-Pt), and [Pt(C4)Cl2] (C4-Pt) with 3-(1H-benzo[d]imidazol-2-yl)-2H-chromen-2-imine (C1), 6-bromo-3-(pyridin-2-yl)-2H-chromen-2-imine (C2), 6-chloro-3-(pyridin-2-yl)-2H-chromen-2-imine (C3), and 5,7-dichloro-3-(pyridin-2-yl)-2H-chromen-2-imine (C4), were first designed and synthesized as mitochondria-targeting antitumor agents. C1-Pt − C4-Pt showed cytotoxic activity against A549 and A549/DDP cancer cells, and most 6-chloro-substituted groups had stronger cytotoxicity than did the benzopyran Pt(II)-substituted ones. Significantly, C3-Pt was much more effective on cisplatin-resistant A549/DDP tumor cells (IC50 = 0.15 ± 0.03 μM) than C1-Pt, C2-Pt and C4-Pt. Interestingly, C1-Pt − C4-Pt exhibited much lower cytotoxicity against normal cells (IC50 > 100 μM) than against A549/DDP tumor cells. Additionally, mechanistic studies showed that C2-Pt and C3-Pt significantly inhibited cell growth in A549/DDP cells in S phase, accumulated more in mitochondria than in nuclei, and caused the loss of mitochondrial membrane potential, concurrently targeting mitochondria.

中文翻译：

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四种铂 (II) 配合物与靶向线粒体的苯并吡喃衍生物的合成、结构和抗癌潜力

摘要 四种新型苯并吡喃-铂 (Pt) 配合物 [Pt(C1)Cl2]⋅CH3OH (C1-Pt)、[Pt(C2)Cl2] (C2-Pt)、[Pt(C3)Cl2] (C3-Pt) ), 和 [Pt(C4)Cl2] (C4-Pt) 与 3-(1H-benzo[d]imidazol-2-yl)-2H-chromen-2-imine (C1), 6-bromo-3-( pyridin-2-yl)-2H-chromen-2-imine (C2), 6-chloro-3-(pyridin-2-yl)-2H-chromen-2-imine (C3), 和 5,7-dichloro- 3-(pyridin-2-yl)-2H-chromen-2-imine (C4)，首先被设计和合成为线粒体靶向抗肿瘤剂。C1-Pt - C4-Pt 对 A549 和 A549/DDP 癌细胞显示出细胞毒活性，并且大多数 6-氯取代基团比苯并吡喃 Pt(II)-取代基团具有更强的细胞毒性。值得注意的是，C3-Pt 对顺铂耐药的 A549/DDP 肿瘤细胞（IC50 = 0.15 ± 0.03 μM）比 C1-Pt、C2-Pt 和 C4-Pt 更有效。有趣的是，C1-Pt - C4-Pt 对正常细胞的细胞毒性（IC50 > 100 μM）远低于对 A549/DDP 肿瘤细胞的细胞毒性。此外，机理研究表明，C2-Pt 和 C3-Pt 显着抑制 S 期 A549/DDP 细胞的细胞生长，在线粒体中的积累多于细胞核，并导致线粒体膜电位的丧失，同时靶向线粒体。