Indole derivatives targeting colchicine binding site as potential anticancer agents

Abstract

Microtubules are appealing as intracellular targets for anticancer activity due to their importance in cell division. Three important binding sites are present on the tubulin protein: taxane, vinca, and colchicine binding sites (CBS). Many USFDA-approved drugs such as paclitaxel, ixabepilone, vinblastine, and combretastatin act by altering the dynamics of the microtubules. Additionally, a large number of compounds have been synthesized by medicinal chemists around the globe that target different tubulin binding sites. Although CBS inhibitors have proved their cytotoxic potential, no CBS-targeting drug had been able to reach the market. Several studies have reported design, synthesis, and biological evaluation of indole derivatives as potential anticancer agents. These compounds have been shown to inhibit cancer cell proliferation, induce apoptosis, and disrupt microtubule formation. Moreover, the binding affinity of these compounds to the CBS has been demonstrated using molecular docking studies and competitive binding assays. The present work has reviewed indole derivatives as potential colchicine-binding site inhibitors. The structure-activity relationship studies have revealed the crucial pharmacophoric features required for the potent and selective binding of indole derivatives to the CBS. The development of these compounds with improved efficacy and reduced toxicity could potentially lead to the development of novel and effective cancer therapies.

Keywords: cancer; colchicine binding site; indole; tubulin.