Discovery of 1,4-pentadien-3-one derivatives containing quinoxaline scaffolds as potential apoptosis inducers.
Xu TangJun HeQin LiXuemei TangMei ChenGefei HaoZiyou HuaiYinjin HuangWei XuePublished in: Future medicinal chemistry (2020)
Aim: To synthesize novel antiproliferative agents. Results & methodology: A variety of 1,4-pentadien-3-one derivatives bearing quinoxaline scaffolds was designed and synthesized and their antiproliferative activities were evaluated. Notably, compounds N3 and N4 exhibited markedly greater antiproliferative activities against SMMC-7721 cells in vitro compared with the well-known antitumor drug gemcitabine. The mechanistic investigation showed that compounds N3 and N4 induced SMMC-7721 cell apoptosis by regulating the expression levels of apoptosis-related proteins. In addition, the molecular docking model further revealed that compound N3 could be a potential peroxisome proliferator-activated receptor inhibitor. Conclusion: These compounds might serve as bioactive fragments and lead compounds for developing more potent apoptosis inducers.
Keyphrases
- cell cycle arrest
- molecular docking
- endoplasmic reticulum stress
- cell death
- oxidative stress
- induced apoptosis
- pi k akt
- tissue engineering
- poor prognosis
- molecular dynamics simulations
- cell proliferation
- diabetic rats
- small molecule
- high glucose
- squamous cell carcinoma
- single cell
- human health
- radiation therapy
- locally advanced
- long non coding rna