Indole Molecules As Inhibitors Of Tubulin Polymerization: Potential New Anticancer Agents

Abstract

Agents that interfere with tubulin function have a broad anti-tumor spectrum and they represent one of the most significant classes of anticancer agents. In the past few years, several small synthetic molecules that have an indole nucleus as a core structure have been identified as tubulin inhibitors. Among these, several aroylindoles, arylthioindoles, diarylindoles and indolylglyoxyamides have shown good inhibition towards the tubulin polymerization. This article reviews the synthesis, biological activities and SARs of these main classes of indoles. Brief mention has also been made about the fused indole analogs as tubulin inhibitors.

Applications of Bartoli indole synthesis

“…Bicyclic aromatic heterocycles containing nitrogen atoms, such as quinolines, isoquinolines, and indoles are present in all classes of organic compounds in the biological and medicinal arena. [3][4][5][6][7][8][9][10][11] In particular, over ten thousand biologically active indole derivatives have been identified to date. Of those, over 200 are currently marked as drugs or undergoing clinical trials.…”

Synthesis and biological evaluation of indole-based, anti-cancer agents inspired by the vascular disrupting agent 2-(3′-hydroxy-4′-methoxyphenyl)-3-(3″,4″,5″-trimethoxybenzoyl)-6-methoxyindole (OXi8006)

“…10–12 VDAs can be further divided into two distinct groups: biologics and small-molecules. One strategy focuses on the development of indole-based small-molecule VDAs that bind at the colchicine site, named after the natural product originally described as binding at the site (Figure 1) 13 and whose interaction with tubulin led to the original isolation of the protein. 14 Synthetic and biological studies with indole-based, colchicine site VDAs were originally prompted by the discovery of the potent natural products combretastatin A-4 ( CA4 ) and combretastatin A-1 ( CA1 ) that were isolated from the African bush willow tree, Combretum caffrum , by Pettit and co-workers (Figure 1).…”

Unconventional Knoevenagel-type indoles: Synthesis and cell-based studies for the identification of pro-apoptotic agents

“…Indole derivatives have been described as useful chemical templates in different therapeutic areas, including the treatment of neurodegenerative diseases [3][4][5], psychiatric disorders [6] and inflammation [7,8]. Moreover, indole derivatives were found to be endowed with antiviral [9], antioxidant [10], antiplasmodial [11], antiproliferative and antitumor efficacy [12][13][14][15][16][17][18][19][20]. Recently induction of methuosis, which is one of the most recently acknowledged nonapoptotic cell death phenotype involving the accumulation of cytoplasmic vacuoles derived from macropinosomes, was identified as the mechanism of action of conjugated 3-vinyl indoles [21].…”