Breast cancer is one of the most common cancers in the world, and pro-apototic drugs activating the apoptotic pathway are a strategy for anticancer therapy. To explore new antineoplastic agents, a series of novel mono-indolylbenzoquinone derivatives have been designed and synthesized. Compared with the lead bis-indolylbenzoquinones, most of the novel mono-indolylbenzoquinone derivatives have significantly increased their activity against A549, HeLa, and especially, MDA-MB-231 cell lines. Among them, 10d has the lowest IC₅₀ value of 70 nM on MDA-MB-231 cells. Moreover, its oral toxicity is extremely low with an LD₅₀ value of 374 mg/kg and no obvious liver and kidney damage to mice. 10d down-regulated Bcl-2, up-regulated Bax, and increased the release of cytochrome C, caspase3 and 9. 10d also up-regulated the expression of p53, catalase, and HTRA2/Omi. Therefore, 10d may exert its anticancer activity by activating apoptotic pathway and p53 expression. In vivo, 10d suppressed breast cancer 4T1 tumor growth with 36% inhibition ratio of tumor by intraperitoneal injection in mice. Furthermore, a cross-linked cyanoacrylate (CA)-based local sustained-release drug delivery systems (LSRDDSs) improved 10d anticancer activity to 49.8% inhibition of tumor growth. Taken together, 10d could be a promising drug candidate for clinical development to treat metastatic breast cancer.

乳腺癌是世界上最常见的癌症之一，激活细胞凋亡途径的促凋亡药物是抗癌治疗的一种策略。为了探索新型抗肿瘤药物，我们设计并合成了一系列新型单吲哚基苯醌衍生物。与先导双吲哚基苯醌相比，大多数新型单吲哚基苯醌衍生物对A549、HeLa，尤其是MDA-MB-231细胞系的活性显着增强。其中， 10d在MDA-MB-231细胞上的IC ₅₀值最低，为70 nM。而且其口服毒性极低，LD ₅₀值为374 mg/kg，对小鼠无明显肝、肾损害。 10d下调 Bcl-2，上调 Bax，并增加细胞色素 C、caspase3 和 9 的释放。10d还上调 p53、过氧化氢酶和 HTRA2/Omi 的表达。因此， 10d可能通过激活细胞凋亡途径和p53表达来发挥其抗癌活性。在体内，小鼠腹腔注射10d可抑制乳腺癌4T1肿瘤生长，抑瘤率为36%。此外，基于交联氰基丙烯酸酯（CA）的局部缓释药物递送系统（LSRDDS）将10天的抗癌活性提高到对肿瘤生长的抑制率达到49.8%。总而言之， 10d可能是一种有前途的候选药物，可用于治疗转移性乳腺癌的临床开发。