Novel nitrogen mustard-artemisinin hybrids with potent anti-leukemia action through DNA damage and activation of GPx.

The incidence of various types of cancers is increasing every year. Among these, leukemia is extremely common, and thus, developing novel drugs to combat leukemia is crucial. In this study, we designed and synthesized several hybrids and obtained a new lead molecule 5a, with a strong therapeutic effect on leukemia. The results indicated that most hybrids effectively inhibited the growth of leukemia cells, HCT-116, and A549 cancer cells with an IC50 of <10 µM. Among these hybrids, 5a and 4h showed significant anticancer activity against CCRF-CEM, with IC50 values of 0.895 µM and 0.555 µM, respectively. Particularly, 5a had lower toxicity to L02 than chlorambucil (CLB) and doxorubicin (Dox), and the high selectivity was also reflected in the normal human B lymphoblast cell line (IM9). Upon investigating the mechanism of action, we found that 5a downregulated Bcl-2 and caused DNA double-stranded breaks (DSBs) to induce several genotoxic stress responses. The results of the flow cytometry assay showed that 5a was a non-specific molecule in the cell cycle. Furthermore, 5a did not affect total ROS levels but significantly improved the activity of glutathione peroxidase (GPx). Preliminary studies showed that nitrogen mustard exerted an efficient effect, and 5a can combine the advantages of artemisinin and nitrogen mustard and exhibit effects superior to either. This study showed that 5a should be further investigated as a therapeutic compound against leukemia.

Novel artemisinin derivatives with potent anticancer activities and the anti-colorectal cancer effect by the mitochondria-mediated pathway.

Many artemisinin derivatives have good inhibitory effects on malignant tumors. In this work, a novel series of artemisinin derivatives containing piperazine and fluorine groups were designed and synthesized and their structures were confirmed by 1H NMR, 13C NMR and HRMS technologies. The in vitro cytotoxicity against various cancer cell lines was evaluated. Among the derivatives, compound 12h was found to exhibit not only the best activity against HCT-116 cells (IC50 = 0.12 ± 0.05 µM), but also low toxicity against normal cell line L02 (IC50 = 12.46 ± 0.10 µM). The mechanisms study revealed that compound 12h caused the cell cycle arrest in G1 phase, induced apoptosis in a concentration-dependent manner, significantly reduced mitochondrial membrane potential, increased intracellular ROS and Ca2+ levels, up-regulated the expression of Bax, cleaved caspase-9, cleaved caspase-3, and down-regulated the expression of Bcl-2 protein. A series of analyses confirmed that 12h can inhibit HCT-116 cells migration and induce apoptosis by a mechanism of the mitochondria-mediated pathway in the HCT-116 cell line. The present work indicates that compound 12h may merit further investigation as a potential therapeutic agent for colorectal cancer.

Facile Fabrication of Transparent and Upconversion Photoluminescent Nanofiber Mats with Tunable Optical Properties.

A facile fabrication strategy of transparent and upconversion photoluminescent nylon 6 (PA6) nanofiber mats was developed based on PA6 nanofiber mats, carboxylic acid-functionalized upconversion nanoparticles (UCNP-COOH), and poly(methyl methacrylate) (PMMA) solution. UCNP-COOH were prepared by a solvothermal method, followed by the ligand exchange process. The electrospinning method and the spin-coating process were employed to combine PA6 nanofiber mats with UCNP-COOH and PMMA to introduce upconversion photoluminescent properties and transparency into the nanocomposite mats, respectively. The prepared UCNP-COOH/PA6/PMMA nanofiber mats are transparent and exhibit green emission, which are similar to UCNP-COOH when they were excited under 980 nm laser. The upconversion luminescent intensity of the functional nanofiber mats can be tailored by adjusting the weight fraction of UCNP-COOH as fillers. This facile strategy can be readily used to other types of intriguing nanocomposites for diverse applications.