Combined Molecular Docking, 3D-QSAR, and Pharmacophore Model: Design of Novel Tubulin Polymerization Inhibitors by Binding to Colchicine-binding Site

2015 ◽  
Vol 86 (4) ◽  
pp. 731-745 ◽  
Author(s):  
Dong-Dong Li ◽  
Ya-Juan Qin ◽  
Xin Zhang ◽  
Yong Yin ◽  
Hai-Liang Zhu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Site ◽  
Pharmacophore Model ◽  
3D Qsar ◽  
Tubulin Polymerization ◽  
Model Design ◽  
Colchicine Binding Site ◽  
Tubulin Polymerization Inhibitors

scholarly journals Identification of potential tubulin polymerization inhibitors by 3D-QSAR, molecular docking and molecular dynamics

RSC Advances ◽  
2017 ◽  
Vol 7 (61) ◽  
pp. 38479-38489 ◽  
Author(s):  
Tian Chi Wang ◽  
Li Ping Cheng ◽  
Xin Ying Huang ◽  
Lei Zhao ◽  
Wan Pang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Binding Site ◽  
3D Qsar ◽  
Tubulin Polymerization ◽  
Tubulin Polymerization Inhibitors

View of the correlation between experimental and predicted pIC50c values, and the compound 22c docked into the binding site of 3UT5.

scholarly journals Design, eco-friendly synthesis, molecular modeling and anticancer evaluation of thiazol-5(4H)-ones as potential tubulin polymerization inhibitors targeting the colchicine binding site

RSC Advances ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 2791-2811 ◽  
Author(s):  
Abeer M. El-Naggar ◽  
Ibrahim H. Eissa ◽  
Amany Belal ◽  
Amira A. El-Sayed
Keyword(s):  
Molecular Modeling ◽  
Cancer Treatment ◽  
Binding Site ◽  
Therapeutic Approach ◽  
Tubulin Polymerization ◽  
Colchicine Binding Site ◽  
Tubulin Polymerization Inhibitors

In recent years, suppressing tubulin polymerization has been developed as a therapeutic approach for cancer treatment.

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.

Synthesis, Anti-proliferative Evaluation, and Molecular Docking Studies of 3-(alkylthio)-5,6-diaryl-1,2,4-triazines as Tubulin Polymerization Inhibitors

2019 ◽  
Vol 16 (11) ◽  
pp. 1194-1201 ◽  
Author(s):  
Farhad Saravani ◽  
Ebrahim Saeedian Moghadam ◽  
Hafezeh Salehabadi ◽  
Seyednasser Ostad ◽  
Morteza Pirali Hamedani ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Cytotoxic Activity ◽  
Binding Site ◽  
Cell Line ◽  
Cell Lines ◽  
Tubulin Polymerization ◽  
Adenocarcinoma Cell Line ◽  
Adenocarcinoma Cell ◽  
Colchicine Binding Site ◽  
Anti Cancer

Background: The role of microtubules in cell division and signaling, intercellular transport, and mitosis has been well known. Hence, they have been targeted for several anti-cancer drugs. Methods: A series of 3-(alkylthio)-5,6-diphenyl-1,2,4-triazines were prepared and evaluated for their cytotoxic activities in vitro against three human cancer cell lines; human colon carcinoma cells HT-29, human breast adenocarcinoma cell line MCF-7, human Caucasian gastric adenocarcinoma cell line AGS as well as fibroblast cell line NIH-3T3 by MTT assay. Docking simulation was performed to insert these compounds into the crystal structure of tubulin at the colchicine binding site to determine a probable binding model. Compound 5d as the most active compound was selected for studying of microtubule disruption. Results: Compound 5d showed potent cytotoxic activity against all cell lines. The molecular modeling study revealed that some derivatives of triazine strongly bind to colchicine binding site. The tubulin polymerization assay kit showed that the cytotoxic activity of 5d may be related to inhibition of tubulin polymerization. Conclusion: The cytotoxicity and molecular modeling study of the synthesized compounds with their inhibition activity in tubulin polymerization demonstrate the potential of triazine derivatives for development of new anti-cancer agents.

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