Sixteen furoxan-based nitric oxide (NO) releasing coumarin derivatives (6a-c, 8a-g, 10a, 13a,b, 15, and 17a,b) were designed, synthesized, and evaluated against the A549, HeLa, A2780, A2780/CDDP, and HUVEC cell lines. Most derivatives displayed potent antiproliferation activities. Among them, 8b exhibited the strongest antiproliferation activity on the four sensitive cell lines mentioned above and three drug resistant tumor cell lines A2780/CDDP, MDA-MB-231/Gem, and SKOV3/CDDP with IC50 values from 14 to 53 nM and from 62 to 140 nM, respectively. Furthermore, 8b inhibited the growth of A2780 in vivo and displayed lower toxicity on nontumorigenesis T29, showing good selectivity against malignant cells in vitro. Preliminary pharmacological studies showed that 8b induces apoptosis, arrests the cell cycle at the G2/M phase in the A2780 cell line, and disrupts the phosphorylation of MEK1 and ERK1. Overall, the NO-releasing capacity and the inhibition of ERK/MAPK pathway signaling may explain the potent antineoplastic activity of these compounds.

Telomere and telomerase play important roles in abnormal cell proliferation, metastasis, stem cell maintenance, and immortalization in various cancers. Therefore, designing of drugs targeting telomerase and telomere is of great significance. Over the past two decades, considerable knowledge regarding telomere and telomerase has been accumulated, which provides theoretical support for the design of therapeutic strategies such as telomere elongation. Therefore, the development of telomere‐based therapies such as nucleoside analogs, non‐nucleoside small molecules, antisense technology, ribozymes, and dominant negative human telomerase reverse transcriptase are being prioritized for eradicating a majority of tumors. While the benefits of telomere‐based therapies are obvious, there is a need to address the limitations of various therapeutic strategies to improve the possibility of clinical applications. In this study, current knowledge of telomere and telomerase is discussed, and therapeutic strategies based on recent research are reviewed.

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Studies have shown that the abnormal activation of the NLRP3 inflammasome is involved in a variety of inflammatorybased diseases. In this study, a high content screening model targeting the activation of inflammasome was first established and pterostilbene was discovered as the active scaffold. Based on this finding, total of 50 pterostilbene derivatives were then designed and synthesized. Among them, compound 47 was found to be the best one for inhibiting cell pyroptosis [inhibitory rate (IR) = 73.09% at 10 μM], showing low toxicity and high efficiency [against interleukin-1β (IL-1β): half-maximal inhibitory concentration (IC 50 ) = 0.56 μM]. Further studies showed that compound 47 affected the assembly of the NLRP3 inflammasomes by targeting NLRP3. The in vivo biological activity showed that this compound significantly alleviated dextran sodium sulfate (DSS)-induced colitis in mice. In general, our study provided a novel lead compound directly targeting the NLRP3 protein, which is worthy of further research and structural optimization.