Structure-Activity Relationships and Antiproliferative Effects of 1,2,3,4-4H-Quinoxaline Derivatives as Tubulin Polymerization Inhibitors

2021 ◽  
pp. 104793
Author(s):  
Tingting Liang ◽  
Xiaomin Zhou ◽  
Lu Lu ◽  
Haiyang Dong ◽  
Yanan Zhang ◽  
...  
Keyword(s):  
Tubulin Polymerization ◽  
Antiproliferative Effects ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Quinoxaline Derivatives ◽  
Tubulin Polymerization Inhibitors

Synthesis and structure–activity relationships of 1,2,4-triazoles as a novel class of potent tubulin polymerization inhibitors

2005 ◽  
Vol 15 (23) ◽  
pp. 5154-5159 ◽  
Author(s):  
Xiaohu Ouyang ◽  
Xiaoling Chen ◽  
Evgueni L. Piatnitski ◽  
Alexander S. Kiselyov ◽  
Hai-Ying He ◽  
...  
Keyword(s):  
Tubulin Polymerization ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Tubulin Polymerization Inhibitors

The Structure of MT189-Tubulin Complex Provides Insights into Drug Design

2019 ◽  
Vol 16 (9) ◽  
pp. 1069-1073
Author(s):  
Zhongping Li ◽  
Lingling Ma ◽  
Chengyong Wu ◽  
Tao Meng ◽  
Lanping Ma ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Binding Site ◽  
Complex Structure ◽  
Microtubule Assembly ◽  
Tubulin Polymerization ◽  
Colchicine Binding Site ◽  
Structure Activity ◽  
Tubulin Tyrosine Ligase ◽  
Tubulin Polymerization Inhibitors

Background: Drugs that interfere with microtubule dynamics are used widely in cancer chemotherapy. Microtubules are composed of αβ-tubulin heterodimers, and the colchicine binding site of tubulin is an important pocket for designing tubulin polymerization inhibitors. We have previously designed and synthesized a series of colchicine binding site inhibitors (CBSIs). However, these compounds showed no anticancer activity in vivo. Then, we have used a deconstruction approach to obtain a new derivative MT189, which showed in vivo anticancer activity. Methods: We crystallized a protein complex including two tubulins, one stathmin-like domain of RB3 and one tubulin tyrosine ligase, and soaked MT189 into the crystals. We collected the diffraction data and determined the tubulin-MT189 structure to 2.8 Å. Results: Here, we report the crystal structure of tubulin complexed with MT189, elucidate how the small-molecular agent binds to tubulin and inhibits microtubule assembly, and explain previous results of the structure-activity-relationship studies. Conclusion: The tubulin-MT189 complex structure reveals the interactions between this agent and tubulin and provides insights into the design of new derivatives targeting the colchicine binding site.

scholarly journals Structure–Activity Relationships and in Vivo Evaluation of Quinoxaline Derivatives for PET Imaging of β-Amyloid Plaques

2013 ◽  
Vol 4 (7) ◽  
pp. 596-600 ◽  
Author(s):  
Masashi Yoshimura ◽  
Masahiro Ono ◽  
Kenji Matsumura ◽  
Hiroyuki Watanabe ◽  
Hiroyuki Kimura ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Amyloid Plaques ◽  
In Vivo Evaluation ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Quinoxaline Derivatives ◽  
Β Amyloid
Sign in / Sign up

Export Citation Format

Share Document