High levels of both nitric oxide (NO) and reactive oxygen species (ROS) could acts as pro-apoptotic signals in cancerous cells. In this study, we conjugated diazeniumdiolates (NONOates), an important class of NO donors, with a natural occurring plumbagin (PL) which is primarily an excellent ROS inducer. Herein, a total of 12 novel plumbagin/NONOate hybrids have been synthesized and evaluated for their inhibitory effects on a panel of human cancer cell lines (MDA-MB-231, A549, HepG2 and HCT-116 cells) and two normal human cells (HK-2 and WRL-68 cells). Among them, compounds 10a and 10b demonstrated superior potencies compared to their parent compound (IC₅₀ values of 3.48–6.68 μM) against the above cancer cell lines but weak inhibitory effects on normal cells. In concordance with their selective cytotoxicities, 10a and 10b released higher level of NO in cancer cells than normal cells. Besides, the potent compound 10a induced apoptosis of A549 cells in a concentration-dependent manner and resulted in more ROS generation compared with the parent compound plumbagin.

高水平的一氧化氮（NO）和活性氧（ROS）可能在癌细胞中充当促凋亡信号。在这项研究中，我们将一类重要的NO供体diazeniumdiolates（NONOates）与天然存在的铅蛋白（PL）结合在一起，而后者主要是出色的ROS诱导剂。本文合成了总共12种新颖的plumbagin / NONOate杂种并评估了它们对一组人类癌细胞系（MDA-MB-231，A549，HepG2和HCT-116细胞）和两个正常人类细胞（ HK-2和WRL-68电池）。其中，化合物10a和10b与母体化合物相比具有更强的效力（IC ₅₀对上述癌细胞系的抗药性值为3.48–6.68μM），但对正常细胞的抑制作用较弱。与它们的选择性细胞毒性一致，10a和10b在癌细胞中释放的NO水平高于正常细胞。此外，与母体化合物plumbagin相比，有效的化合物10a以浓度依赖的方式诱导A549细胞凋亡，并导致更多的ROS产生。