Ligands of the colchicine site of tubulin: A common pharmacophore and new structural classes

Abstract

Structure-activity relationships for ligands of the colchicine site of tubulin were analyzed based on their common pharmacophore. The role of the elucidation of the three dimensional structure of the colchicine site of tubulin on the development of studies aimed at the search for the ligands of this site is analyzed.

Novel Aldimine‐Type Schiff Bases of 4‐Amino‐5‐[(3,4,5‐trimethoxyphenyl)methyl]‐1,2,4‐triazole‐3‐thione/thiol: Docking Study, Synthesis, Biological Evaluation, and Anti‐Tubulin Activity

“…Literature review revealed that there are at least three pharmacophore models for CBSIs. The first model consists of three hydrogen bond acceptors (Cysβ241, Leuβ252, Aspβ251, Alaβ250, and Valα181), one hydrogen bond donor (Thrα179), two hydrophobic centers, and one planar group . The second model is composed of one hydrogen bond acceptor (Asnα101), one hydrogen bond donor, one hydrophobic feature, and one aromatic ring feature while the third model is made up of three hydrogen bond acceptors (Valα181, Leuβ252, and Cysβ241), a hydrogen bond donor (Thrα179), and a hydrophobic skeleton with four hydrophobic centers .…”

Synthesis of Novel Chromenes as Cytotoxic Agents

“…[3,2-e] [1,2,4]triazolo [1,5-c]pyrimidines (7a and 7b); general procedure A few drops of triethylamine were added to a mixture of 5a or 5b (0.01mol) and the isonicotinic acid hydrazide (1.37 g, 0.01mol) in dioxane (30 mL). The reaction mixture was heated under reflux for 12 h then cooled and poured into ice-cold water.…”

“…(RS)-12-(4-Chlorophenyl)-9-methoxy-2-(pyridin-4-yl)-12H-chromeno [3,2-e] [1,2,4]triazolo [1,5-c] (RS)-12-(4-Chlorophenyl)-9-ethoxy-2-(pyridin-4-yl)-12Hchromeno [3,2e] [1,2,4] triazolo [1,5-c] …”

“…The action of colchicine is due to binding at a particular site of tubulin (the colchicine binding site), resulting in deformation of the α, β-dimer structure, which hinders the tubulin assembly into microtubules. 1,2 In recent years, several new structurally related classes of colchicine have been synthesised. For example, compound I ( Fig.…”

Diels-alder reaction as a synthetic approach to bicyclo[3.3.1]nonane colchicine analogs

“…In the framework of our studies aimed at synthesizing compounds possessing antitumor activity we try to obtain bioisosteres of the antitumor drug Colchicine [1] on the basis of cage-like structures. The results of computer-assisted molecular modeling showed that compounds of the general formula I should quite effectively bind to tubulin which is a molecular target of Colchicine in vivo.…”