As a continuation of our research on developing potent and potentially safe antineoplastic agents, a set of forty five sulfur-containing shikonin oxime derivatives were synthesized and evaluated for their in vitro cytotoxic activity against human colon cancer (HCT-15), gastric carcinoma (MGC-803), liver (Bel7402), breast (MCF-7) cancer cells and human skin fibroblast (HSF) cells. All the synthesized compounds exhibited potent cytotoxic activity selectively towards HCT-15 cells and did not display apparent toxicity to the normal HSF cells, some of which were more or comparatively effective to the parent compound against HCT-15, MGC-803 and Bel7402 cells. The most active agent 9m displayed high potency against human cancer cells with IC₅₀ ranging from 0.27 ± 0.02 to 9.23 ± 0.12 μM. The structure-activity relationships (SARs) studies suggested that the nature of substituent group in the side chain is important for antitumor potency in vitro. Additionally, nitric oxide release studies revealed that the amount of nitric oxide generated from these oxime derivatives was relatively low. Furthermore, cellular mechanism investigations indicated that compound 9m could arrest cell cycle at G1 phase and induce a strong apoptotic response in HCT-15 cells. Moreover, western blot studies revealed that compound 9m induced apoptosis through the down-regulation of Bcl-2 and up-regulation of Bax, caspase 3 and 9. For all these reasons, compound 9m hold promising potential as antineoplastic agent.

作为我们对开发有效且潜在安全的抗肿瘤药的研究的继续，合成了一组45种含硫的紫草素肟衍生物，并评估了其对人结肠癌（HCT-15），胃癌（MGC）的体外细胞毒活性。 -803），肝（Bel7402），乳腺癌（MCF-7）癌细胞和人皮肤成纤维细胞（HSF）细胞。所有合成的化合物均选择性地对HCT-15细胞显示出有效的细胞毒活性，对正常的HSF细胞没有明显的毒性，其中一些对母体化合物对HCT-15，MGC-803和Bel7402细胞具有更高或相对的效力。活性最强的9m药物以IC ₅₀表现出对人类癌细胞的高效力范围从0.27±0.02到9.23±0.12μM。结构-活性关系（SARs）研究表明，侧链取代基的性质对于体外抗肿瘤药效很重要。另外，一氧化氮的释放研究表明，由这些肟衍生物产生的一氧化氮的量相对较低。此外，细胞机制研究表明，化合物9m可以在G1期阻滞细胞周期，并在HCT-15细胞中诱导强烈的凋亡反应。此外，蛋白质印迹研究表明，化合物9m通过Bcl-2的下调和Bax，胱天蛋白酶3和9的上调诱导细胞凋亡。由于所有这些原因，化合物9m 具有抗肿瘤药的潜力。