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三种新型有机锡(IV)羧酸酯配合物的合成及抗肿瘤活性研究。

Synthesis and anti-tumor activities of three newly designed organotin(IV) carboxylates complexes.

机构信息

School of Preclinical Medicine, Wannan Medical College, Wuhu 241002, People's Republic of China.

School of pharmacy, Wannan Medical College, Wuhu 241002, People's Republic of China.

出版信息

J Inorg Biochem. 2024 Sep;258:112609. doi: 10.1016/j.jinorgbio.2024.112609. Epub 2024 May 18.

Abstract

Three distinctive end group-containing organotin (IV) carboxylates complexes (YDCOOSn, CLCOOSn and BZCOOSn) were designed and synthesized. Together with theoretical calculations, a thorough examination was carried out to investigate the photophysical properties of these compounds. The cytotoxicity of the synthesized compounds was tested using normal cell line GES-1 and was assessed against four cancer cell lines (A549, Hela, H1299 and HepG2). The outcomes of the experiments demonstrated that these complexes had superior selectivity than cisplatin towards cancerous cells, particularly in the A549 cell line. BZCOOSn was selected as a candidate compound for additional research because it exhibited the lowest IC value and the most impressive inducing effect on cell death and G2/M phase arrest. Increased caspase-3 and -9 enzyme activity, a decline in mitochondrial membrane potential (MMP), characteristic nuclear apoptotic morphology, and an accumulation of intracellular reactive oxygen species (ROS) were seen in A549 exposed to BZCOOSn. These findings demonstrated that BZCOOSn exhibited strong cytotoxicity by triggering cell death in A549 via the mitochondrial route. Furthermore, using the scratch wound healing assay, it was discovered that BZCOOSn reduced the migration of A549 cancerous cells. These data all pointed to BZCOOSn as a possible candidate for more research and development as a chemotherapeutic drug.

摘要

三种具有独特端基的含锡(IV)羧酸盐配合物(YDCOOSn、CLCOOSn 和 BZCOOSn)被设计和合成。通过理论计算,对这些化合物的光物理性质进行了全面的研究。通过正常细胞系 GES-1 测试了合成化合物的细胞毒性,并对四种癌细胞系(A549、Hela、H1299 和 HepG2)进行了评估。实验结果表明,这些配合物对癌细胞的选择性优于顺铂,特别是在 A549 细胞系中。BZCOOSn 被选为进一步研究的候选化合物,因为它表现出最低的 IC 值和对细胞死亡和 G2/M 期阻滞的最显著诱导作用。在 BZCOOSn 处理的 A549 中观察到 caspase-3 和 -9 酶活性增加、线粒体膜电位 (MMP) 下降、特征性核凋亡形态和细胞内活性氧 (ROS) 积累。这些发现表明,BZCOOSn 通过线粒体途径触发 A549 细胞死亡表现出强烈的细胞毒性。此外,通过划痕愈合实验发现 BZCOOSn 减少了 A549 癌细胞的迁移。所有这些数据都表明 BZCOOSn 可能成为一种有前途的候选药物,用于进一步的研究和开发作为化疗药物。

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