沙利多米 (THD) 及其类似物最近被报道为不同类型实体瘤的有希望治疗药物，因其抗血管生成效果。在本文中，我们合成了一种新的 THD 类似物 (TA)，并使用红外线、质谱、元素分析、1H 和13C NMR 等不同技术确认了其化学性质。为了增加溶解度和抗癌功效，我们使用了一种新的油水纳米乳 (NE) 在类似物的配方中。我们对新配方的表面电荷、大小、稳定性、红外线、场发射透射电子显微镜、体外药物释放和物理性质等进行了研究。此外，我们进行了分子对接研究，以预测 THD 和 TA 的抑制活性背后的可能结合模式和分子相互作用。TA 对癌细胞如 MCF-7、HepG2、Caco-2、LNCaP 和 RKO 细胞系的 IC50 值范围从 0.326 到 43.26 微摩尔/毫升不等，表现出显著的细胞毒性活性。该类似物负载后对 MDA-MB-231 和 MCF-7-ADR 细胞株表现出更强的细胞毒性，IC50 值分别为 0.0293 和 0.0208 纳摩尔/毫升。此外，我们进行了细胞周期分析和凋亡的流式细胞术，并在 MDA-MB-231 细胞系中观察到 TGF-β、MCL-1、VEGF、TNF-α、STAT3 和 IL-6 的表达水平受到抑制。新配方大大降低了 TA 的抗癌药量，从微摩尔效率到纳摩尔效率。这表明，合成的类似物在 NE 配方中表现出高效性，并证明了其对三阴性乳腺癌细胞株的有效性。© 2023 Tawfik 等。

Thalidomide (THD) and its analogues were recently reported as a promising treatment for different types of solid tumors due to their antiangiogenic effect.In this work, we synthesized a novel THD analogue (TA), and its chemistry was confirmed with different techniques such as IR, mass spectroscopy, elemental analysis as well as 1H and 13C NMR. To increase solubility and anticancer efficacy, a new oil in water (O/W) nanoemulsion (NE) was used in the formulation of the analogue. The novel formula's surface charge, size, stability, FTIR, FE-TEM, in vitro drug release and physical characteristics were investigated. Furthermore, molecular docking studies were conducted to predict the possible binding modes and molecular interactions behind the inhibitory activities of the THD and TA.TA showed a significant cytotoxic activity with IC50 ranging from 0.326 to 43.26 µmol/mL when evaluated against cancerous cells such as MCF-7, HepG2, Caco-2, LNCaP and RKO cell lines. The loaded analogue showed more potential cytotoxicity against MDA-MB-231 and MCF-7-ADR cell lines with IC50 values of 0.0293 and 0.0208 nmol/mL, respectively. Moreover, flow cytometry of cell cycle analysis and apoptosis were performed showing a suppression in the expression levels of TGF-β, MCL-1, VEGF, TNF-α, STAT3 and IL-6 in the MDA-MB-231 cell line.The novel NE formula dramatically reduced the anticancer dosage of TA from micromolar efficiency to nanomolar efficiency. This indicates that the synthesized analogue exhibited high potency in the NE formulation and proved its efficacy against triple-negative breast cancer cell line.© 2023 Tawfik et al.