Thalidomide and its analogs are immunomodulatory drugs that inhibit the production of certain inflammatory mediators associated with cancer. In the present work, a new series of thalidomide analogs was designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against a panel of four cancer cell lines (HepG-2, HCT-116, PC3 and MCF-7). Compounds 33_h, 33_i, 42_f and 42_h showed strong potencies against all tested cell lines with IC₅₀ values ranging from 14.63 to 49.90 µM comparable to that of thalidomide (IC₅₀ values ranging from 32.12 to 76.91 µM). The most active compounds were further evaluated for their in vitro immunomodulatory activities via estimation of human tumor necrosis factor alpha (TNF-α), human caspase-8 (CASP8), human vascular endothelial growth factor (VEGF), and nuclear factor kappa-B P65 (NF-κB P65) in HCT-116 cells. Thalidomide was used as a positive control. Compounds 33_h and 42_f showed a significant reduction in TNF-α. Furthermore, compounds 33_i and 42_f exhibited significant elevation in CASP8 levels. Compounds 33_i and 42_f inhibited VEGF. In addition, compound 42_f showed significant decrease in levels of NF-κB p65. Moreover, apoptosis and cell cycle tests of the most active compound 42_f, were performed. The results indicated that compound 42_f significantly induce apoptosis in HCT-116 cells and arrest cell cycle at the G2/M phase.

沙利度胺及其类似物是免疫调节药物，可抑制某些与癌症相关的炎性介质的产生。在目前的工作中，设计并合成了一系列新的沙利度胺类似物以获得新的有效抗肿瘤免疫调节剂。评估合成的化合物对四种癌细胞系（HepG-2，HCT-116，PC3和MCF-7）的细胞毒性活性。化合物33 _ħ，33_我，42 _˚F和42 _ħ表现出较强的效力针对与IC所有测试的细胞系中_50个值范围从14.63到49.90μM比得上的沙利度胺（IC ₅₀值范围从32.12到76.91 µM）。通过评估人类肿瘤坏死因子α（TNF-α），人类caspase-8（CASP8），人类血管内皮生长因子（VEGF）和核因子kappa-B ，进一步评估了活性最高的化合物的体外免疫调节活性。P 65（NF-κB P 65）中的HCT-116细胞。沙利度胺用作阳性对照。化合物33 _ħ和42 _˚F显示出TNF-α一个显著减少。此外，化合物33 _i和42 _f在CASP8水平上显示出明显的升高。化合物33 _i和42 _f抑制VEGF。另外，化合物42 _˚F显示出NF-κBp65的水平显著降低。而且，细胞凋亡和最活跃的化合物的细胞循环试验42 _˚F，进行。结果表明，化合物42 _˚F显著诱导凋亡在HCT-116细胞，并在G2 / M期细胞周期停滞。