scholarly journals A photoaffinity derivative of colchicine: 6'-(4'-azido-2'-nitrophenylamino)hexanoyldeacetylcolchicine. Photolabeling and location of the colchicine-binding site on the alpha-subunit of tubulin.

1985 ◽  
Vol 260 (25) ◽  
pp. 13794-13802
Author(s):  
R F Williams ◽  
C L Mumford ◽  
G A Williams ◽  
L J Floyd ◽  
M J Aivaliotis ◽  
...  
Keyword(s):  
Binding Site ◽  
Alpha Subunit ◽  
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.

Synthesis and tubulin interaction of thiocolchicines containing an isothiocyanato group. Synthesis of C(2)-deuterated and C(2)-14C-labeled 7-isothiocyanatodeacetamidothiocolchicine

1991 ◽  
Vol 56 (11) ◽  
pp. 2306-2312 ◽  
Author(s):  
Anjum Muzaffar ◽  
Ernest Hamel ◽  
Rouli Bai ◽  
Arnold Brossi
Keyword(s):  
Binding Site ◽  
Covalent Bond ◽  
Tubulin Polymerization ◽  
Low Concentration ◽  
Covalent Interaction ◽  
Isotope Label ◽  
Colchicine Binding Site

Synthesis of isothiocyanato substituted thiocolchicines XI - XIV is described. Introduction of an isotope label is demonstrated with the deuterated isothiocyanate XII and the 14C-labeled analog XIII. These isothiocyanates inhibit tubulin polymerization at low concentration. In addition, the 14C-labeled XIII forms covalent bond(s) with tubulin. Unfortunately, the covalent reaction while rapid, is not inhibited by preincubation of tubulin with colchicine. The covalent interaction of XIII with tubulin thus appears to be nonspecific, limiting its use as a marker of the colchicine binding site on tubulin.

scholarly journals Structural insights into targeting of the colchicine binding site by ELR510444 and parbendazole to achieve rational drug design

RSC Advances ◽  
2021 ◽  
Vol 11 (31) ◽  
pp. 18938-18944
Author(s):  
Jia-Hong Lei ◽  
Ling-Ling Ma ◽  
Jing-Hong Xian ◽  
Hai Chen ◽  
Jian-Jian Zhou ◽  
...  
Keyword(s):  
Drug Design ◽  
Binding Site ◽  
Crystal Structures ◽  
Rational Drug Design ◽  
Colchicine Binding Site ◽  
Rational Drug ◽  
Structural Insights

Crystal structures of tubulin complexed with ELR510444 and parbendazole facilitate the design of novel colchicine binding site inhibitors.

Sign in / Sign up

Export Citation Format

Share Document