Synthesis and Antitumor Activity of Novel Amino Glucose Derivative Schiff Base Copper(II) Complexes

doi:10.6023/A25090314

Abstract

Introducing biologically active organic moieties into the coordination field of transition metal complexes has become an effective strategy for improving the selectivity and biocompatibility of metal drugs. In this paper, two ligands L¹and L² with azidoacetylated glucosamine Schiff base structure were designed and synthesized, and then reacts with copper metal salts to synthesize three novel copper complexes. The single crystal structures of ligand L¹and complex 3 were analyzed by X-ray single crystal diffraction technology, and the in vitro cytotoxicity of the compounds on human malignant tumor cell lines and normal cell lines was determined by MTT assay. Among them, complex 2 showed high cytotoxicity against HepG-2 and HeLa cells, approaching or exceeding the value of the positive control, but the toxicity to normal cells was much lower than that of the positive control. The subsequent anti-tumor activity studies of complex 2 with strong cytotoxicity to tumor cells, including apoptosis assessment, intracellular reactive oxygen species generation, mitochondrial membrane potential, cell cycle, cell uptake, migration and invasion, and angiogenesis experiments, further confirmed its inhibitory mechanism on tumor cells. Due to the excellent water solubility of the sugar skeleton in the ligand, complex 2 exhibited good solubility and stability. We further demonstrated through intracellular reactive oxygen species (ROS) production, Hoechst 33342 staining experiment, mitochondrial membrane potential experiment, and Annexin V-mCherry that complex 2 can increase the level of ROS in cancer cells and induce apoptosis through the mitochondrial pathway Cell cycle experiments have shown that complex 2 can delay or inhibit the progression of the cell cycle through the S and G2/M phases. The significant cell uptake results indicated that the high cytotoxicity of complex 2 might be due to its extensive accumulation in HepG-2 cells. In addition, complex 2 can effectively inhibit the migration and invasion of cancer cells, as well as the angiogenesis of normal cell line umbilical vein endothelial cells (HUVEC). Molecular docking results showed that complex 2 has good binding ability with vascular endothelial growth factor receptor 2 (VEGFR-2).

Key words: Crystal structures, Glucosamine, Apoptosis, Cellular Uptake, Migration and Invasion

Cite this article

Gao Chunyan, Cui Xinyue, Wang Kaiyue, Shi Xueyi, He Qing, Zhao Jinzhong, Yue Aiqin, Du Weijun, Zhang Yongpo. Synthesis and Antitumor Activity of Novel Amino Glucose Derivative Schiff Base Copper(II) Complexes[J]. Acta Chimica Sinica, doi: 10.6023/A25090314.

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新型氨基糖类席夫碱铜配合物的合成及抗肿瘤活性研究