Yan Zhang,Yunyun Wang,Yuxun Zhao,Wen Gu,Yongqiang Zhu,Shifa Wang
A series of novel camphor-based pyrimidine derivatives (3a–3x) have been synthesized; their structures were determined by using conventional methods and compound 3f was further confirmed through single crystal XRD analysis. The cytotoxic activity of the target compounds against a panel of human normal (GES-1) and cancer cell lines (MDA-MB-231, RPMI-8226, A549) was evaluated by MTS assay. Here we found that compound 3f exhibited the strongest anti-tumor activity, comparable to that of etoposide, and had much lower cytotoxicity to normal GES-1 cells (IC50 > 50 μM) than the reference drug (IC50 = 8.89 μM). Subsequent mechanism studies in MDA-MB-231 cells revealed that compound 3f caused G0/G1 phase arrest and apoptosis in a dose dependent manner. Moreover, the loss of mitochondrial membrane potential and enhancement of cellular ROS levels were also observed upon 3f treatment, which indicated that 3f exerted cytotoxic activity by a ROS-mediated mitochondrial apoptosis pathway. This result was confirmed by a significant increase in the expression of pro-apoptotic proteins Bax, cytochrome C and caspase-3, and downregulation of anti-apoptosis protein Bcl-2. Overall, 3f can be adopted for further investigation in the development of antitumor agents based on natural products.
The unique properties of covalent organic frameworks (COFs), such as a large specific surface area, good stability and easy functionalization, make them have good potential in the field of separation science. However, the synthesis of chiral COFs is challenging, so the application of COFs in chiral separation is very limited. Here, we show a simple and effective “thiol–ene” click strategy to construct chiral COFs. The chiral COF CTzDva showed high thermal stability and good porosity, prompting us to explore its application in chromatographic separation. The CTzDva-based gas capillary column showed good separation of benzene/cyclohexane, and racemates (citronellal and fenchone). This work provides a promising platform for the synthesis of chiral COFs and expands the application of COFs in the field of separation.
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