22037-03-2Relevant academic research and scientific papers
Synthesis and Biological Evaluation of Selenium-Containing 4-Anilinoquinazoline Derivatives as Novel Antimitotic Agents
An, Baijiao,Wang, Bo,Hu, Jinhui,Xu, Shaoyu,Huang, Ling,Li, Xingshu,Chan, Albert S. C.
, p. 2571 - 2588 (2018/03/26)
Twenty-eight novel selenium-containing 4-anilinoquinazoline derivatives were designed, synthesized, and evaluated as antiproliferative agents. Most of them had significant in vitro activities, particularly for compounds 23a, 25a, and 25d, which also exhibited the most potent antitumor activities against cisplatin-resistant cell lines and the doxorubicin-resistant cell lines, good selectivity toward normal cells, and obvious inhibitory effect on migration of A549 cell lines. Further mechanistic studies revealed that 23a, 25a, and 25d induce G2/M phase arrest and apoptosis in A549 cells, which was associated with a collapse of the mitochondrial membrane potential, alterations in the expression of some cell cycle-related and apoptosis-related proteins, and increasing the intracellular ROS level. Finally, compounds 23a, 25a, and 25d also effectively inhibited the tumor growth in the A549 xenograft model without obvious hints of toxicity. Taken together, these in vitro and in vivo results suggest that 23a, 25a, and 25d may be promising microtubule-stabilizing agents and can be used as a promising lead for the development of new antitumor agents.
The design, synthesis and evaluation of selenium-containing 4-anilinoquinazoline hybrids as anticancer agents and a study of their mechanism
An, Baijiao,Zhang, Shun,Hu, Jinhui,Pan, Tingting,Huang, Ling,Tang, Johnny Cheuk-On,Li, Xingshu,Chan, Albert S. C.
, p. 4701 - 4714 (2018/07/03)
Inhibition of tubulin polymerization is one of the significant strategies in the treatment of cancer. Inspired by the excellent antitumor activity of EP128495 and the beneficial biological activities of selenium compounds, a series of new selenium-containing 4-anilinoquinazoline hybrids were synthesized and evaluated as tubulin polymerization inhibitors. An anti-proliferative activity assay showed that most of the compounds inhibited human sensitive cancer cells at low nanomolar concentrations. A mechanism study revealed that the optimal compound 5a disrupted microtubule dynamics, decreased the mitochondrial membrane potential and arrested HeLa cells in the G2/M phase, finally resulting in cellular apoptosis.
Synthesis and evaluation of new 2-chloro-4-aminopyrimidine and 2,6-dimethyl-4-aminopyrimidine derivatives as tubulin polymerization inhibitors
Xu, Shaoyu,An, Baijiao,Li, Yuxin,Luo, Xunbang,Li, Xingshu,Jia, Xian
supporting information, p. 1769 - 1775 (2018/04/20)
Eighteen new 2-chloro-4-aminopyrimidine and 2,6-dimethyl-4-aminopyrimidine derivatives were synthesized and evaluated as tubulin polymerization inhibitor for the treatment of cancer. Among them, compounds 10, 17, 20 and 21 exhibited potent antiproliferative activities against five human cancer cell lines. Microtubule dynamics assay showed that compound 17 could effectively inhibit tubulin polymerization. Molecular docking studies were also carried out to understand the binding pattern. Further mechanism studies revealed that 17 could induce G2/M phase arrest, disrupt the organization of the cellular microtubule network and induce cell apoptosis and mitochondrial dysfunction.
