结直肠癌（CRC）的化学治疗一直不尽如人意，因此发现更有效的药物对其具有重要意义。根据现有知识，CXCL12/CXCR4轴在肿瘤发生中起着重要作用，而使用AMD3100抑制CXCR4趋化因子受体是癌症治疗中最为广泛的治疗方法之一。在本研究中，我们首次合成了一种强效的CXCR4抑制剂，即N, N''-硫代二碳酰双(N'-(3,4-二甲基苯基)-2,2,2-三氟乙酰胍)（A1）。通过分子对接模拟，我们首先评估了A1与最有效的CXCR4抑制剂的抑制活性。然后，我们使用MTT比色法技术对A1在CT26小鼠CRC细胞上的抗增殖和细胞毒性效应进行了研究，并与对照药物AMD3100进行了比较。我们还利用流式细胞术技术确定了目标化合物IC50对细胞凋亡、细胞周期阻滞和CXCR4表达的影响。我们的研究结果表明，A1在60 μg/mL浓度下对CT26细胞具有细胞毒性效应，在72小时内诱导细胞凋亡和G2/M细胞周期阻滞，而AMD3100在最高800 μg/mL剂量下并没有显示出细胞毒性效应。研究结果还显示，在以100 ng/mL CXCL12处理的CT26细胞中，40 μg/mL浓度的A1显著降低了72小时内的细胞增殖。此外，在以60 μg/mL的A1和100 ng/mL的CXCL12处理的情况下，与对照组（仅以CXCL12处理）相比，CXCR4受体表达的细胞数量显著减少。最终，我们的结果表明，作为一种具有双重功能的全氟化小分子，A1可以通过抑制CXCR4并对肿瘤细胞产生细胞毒性效应来对CRC的治疗有所帮助。Ramaswamy H. Sarma进行了交流。

Chemotherapeutic treatment of colorectal cancer (CRC) has not been satisfactory until now; therefore, the discovery of more efficient medications is of great significance. Based on available knowledge, the CXCL12/CXCR4 axis plays a significant role in tumorigenesis, and inhibition of CXCR4 chemokine receptor with AMD3100 is one of the most known therapeutic modalities in cancer therapy. Herein, N, N''-thiocarbonylbis(N'-(3,4-dimethylphenyl)-2,2,2-trifluoroacetimidamide) (A1) was synthesized as a potent CXCR4 inhibitor. A1 inhibitory activity was first evaluated employing Molecular Docking simulations in comparison with the most potent CXCR4 inhibitors. Then, the antiproliferative and cytotoxic effect of A1 on CT26 mouse CRC cells was investigated by MTT assay technique and compared with those of the control molecule, AMD3100. The impact of the target compounds IC50 on apoptosis, cell cycle arrest, and CXCR4 expression was determined by flow cytometry technique. Our finding demonstrated that A1 induces a cytotoxic effect on CT26 cells at 60 μg/mL concentration within 72 h and provokes cell apoptosis and G2/M cell cycle arrest in comparison with the untreated cells, while AMD3100 did not show a cytotoxic effect up to 800 μg/mL dose. The obtained results show that A1 (at a concentration of 40 μg/mL) significantly reduced the proliferation of CT26 cells treated with 100 ng/mL of CXCL12 in 72 h. Moreover, treatment with 60 μg/mL of A1 and 100 ng/mL of CXCL12 for 72 h significantly decreased the number of cells expressing the CXCR4 receptor compared to the control group treated with CXCL12. Eventually, the obtained results indicate that A1, as a dual-function fluorinated small molecule, may benefit CRC treatment through inhibition of CXCR4 and exert a cytotoxic effect on tumor cells.Communicated by Ramaswamy H. Sarma.