Cancer Research Laboratory, Biomedical Center, Faculty of Medicine, University of Iceland, Sturlugata 8, 101, Reykjavik, Iceland.
Department of Chemistry, Science Institute, University of Iceland, Dunhagi 3, 107 Reykjavík, Iceland.
Dalton Trans. 2022 Aug 30;51(34):13119-13128. doi: 10.1039/d2dt01127a.
Organotin complexes are studied as promising alternatives to the anticancer drug cisplatin. We report two monoorganotin(IV) complexes based on a dibenzyl phosphinoyldithioformate (H-DBPTF) ligand, containing either bromide (Sn-DBPTF-1) or chloride (Sn-DBPTF-2) anions. The complexes were characterized by standard analytical techniques and the structural details of these complexes were elucidated by single crystal X-ray diffraction. Sn-DBPTF-1 was cytotoxic at IC <10 μg mL against cancer cell lines A549 (lung cancer), Aspc-1 (pancreatic cancer), OVCAR-3 (ovarian cancer), T-47D (breast cancer) and HCT116 (colon cancer), and breast epithelial stem cell line D492. The non-tumorigenic breast epithelial cell line MCF-10 was less sensitive at IC = 22 μg mL. Sn-DBPTF-2 had limited cytotoxic effect at IC 13-37 μg mL. Sn-DBPTF-1 induced apoptosis and double-strand DNA breaks. Cell cycle arrest in G2 occurred in HCT116 and accumulation in G1 in Aspc-1. The results indicate that the basic effect of Sn-DBPTF-1 is to induce DNA damage, leading to apoptosis and cell cycle arrest depending on the cell line.
有机锡配合物被研究为顺铂抗癌药物的有前途的替代品。我们报告了两种基于二苄基亚膦酰基二硫代甲酸酯（H-DBPTF）配体的单有机锡（IV）配合物，其中含有溴化物（Sn-DBPTF-1）或氯化物（Sn-DBPTF-2）阴离子。这些配合物通过标准分析技术进行了表征，并通过单晶 X 射线衍射阐明了这些配合物的结构细节。Sn-DBPTF-1 在 IC <10 μg mL 时对癌细胞系 A549（肺癌）、Aspc-1（胰腺癌）、OVCAR-3（卵巢癌）、T-47D（乳腺癌）和 HCT116（结肠癌）和乳腺上皮干细胞系 D492 具有细胞毒性。非致瘤性乳腺上皮细胞系 MCF-10 在 IC = 22 μg mL 时的敏感性较低。Sn-DBPTF-2 在 IC 13-37 μg mL 时具有有限的细胞毒性作用。Sn-DBPTF-1 诱导细胞凋亡和双链 DNA 断裂。HCT116 中发生 G2 期细胞周期阻滞，Aspc-1 中发生 G1 期积累。结果表明，Sn-DBPTF-1 的基本作用是诱导 DNA 损伤，导致细胞凋亡和细胞周期阻滞，具体取决于细胞系。
