Glioblastoma (GBM) is an aggressive malignancy with a high rate of tumor recurrence after treatment with conventional therapies. Parthenolide (PTL), a sesquiterpene lactone extracted from the herb Tanacetum parthenium or feverfew, possesses anticancer properties against a wide variety of solid tumors. In the present study, a series of PTL derivatives were synthesized and screened. An inhibitor, dimethylaminoparthenolide (DMAPT)‑D6, a derivative of the PTL prodrug DMAPT in which the hydrogen of the dimethylamino group is substituted for the isotope deuterium, induced significant cytotoxicity in GBM cells in vitro and induced cell cycle arrest at the S‑phase in a dose‑dependent manner. Furthermore, mechanistic investigation indicated that through increasing the levels of intracellular accumulation of reactive oxygen species (ROS), DMAPT‑D6 triggered DNA damage and finally death receptor‑mediated extrinsic apoptosis in GBM cells, suggesting that DNA damage induced by DMAPT‑D6 initiated caspase‑dependent apoptosis to remove damaged GBM cells. Taken together, these data suggested that ROS accumulation following treatment with DMAPT‑D6 results in DNA damage, and thus, death‑receptor‑mediated apoptosis, highlighting the potential of DMAPT‑D6 as a novel therapeutic agent for the treatment of GBM.

A facile methodology for the construction of a complex heterocycle indazolo-fused quinoxalinone has been developed via an Ugi four-component reaction (U-4CR) followed by an intramolecular Ullmann reaction. The expeditious process features an operationally simple approach, time efficiency, and a broad substrate scope. Biological activity was evaluated and demonstrated that compound 6e inhibits human colon cancer cell HCT116 proliferation with an IC₅₀ of 2.1 μM, suggesting potential applications for developing a drug lead in medicinal chemistry.

Described herein is a concise and practical direct amidation at the C-3 position of quinoxalin-2(1H)-ones through an acid-promoted carbamoylation with isocyanide in water. In this conversion, environmentally friendly water and commercial inexpensive isocyanide were used as a solvent and carbamoylation reagent, respectively. This study not only provides a green and efficient strategy for the construction of 3-carbamoylquinoxalin-2(1H)-one derivatives that can be applied to the synthesis of druglike structures but also expands the application of isocyanide in organic chemistry.

A facile microwave-assisted method for the synthesis of tetramic acid derivatives has been developed through an Ugi/Dieckmann cyclization strategy with DBU. This two-step one-pot procedure afforded the targeted tetramic acid analogues in good yields. With commercially available Ugi starting materials, microwave irradiation, a simple operation, excellent yields, and a broad scope, this reaction has the potential to produce a large number of tetramic acid analogues, which cannot be easily accessed by the classic synthetic methods.

In this study, 2-benzyl-10a-(1H-pyrrol-2-yl)-2,3-dihydropyrazino[1,2-a]indole-1,4,10(10aH)-trione (DHPITO), a previously identified inhibitor against hepatocellular carcinoma cells, is shown to exert its cytotoxic effects by suppressing the proliferation and growth of CRC cells. An investigation of its molecular mechanism confirmed that the cytotoxic activity of DHPITO is mediated through the targeting of microtubules with the promotion of subsequent microtubule polymerisation. With its microtubule-stabilising ability, DHPITO also consistently arrested the cell cycle of the CRC cells at the G2/M phase by promoting the phosphorylation of histone 3 and the accumulation of EB1 at the cell equator, reduced the levels of CRC cell migration and invasion, and induced cellular apoptosis. Furthermore, the compound could suppress both tumour size and tumour weight in a CRC xenograft model without any obvious side effects. Taken together, the findings of the present study reveal the antiproliferative and antitumour mechanisms through which DHPITO exerts its activity, indicating its potential as a putative chemotherapeutic agent and lead compound with a novel structure.