Imidazole antifungals: A review of their Action mechanisms on cancerous cells

Abstract

Imidazoles, together with triazoles, constitute azole sub-group ofantifungal drugs which acts by inhibiting cytochrome P450-dependent enzyme,the lanosterol 14-?-demethylase. In addition to their primary use, when itcomes to additional anti-cancer function, clotrimazole, econazole andketoconazole have come to the fore among the imidazoles. Based on thefindings up to now, although having different effects, disruption of theglycolytic pathway, blockage of Ca2+ influx and nonspecific inhibition ofCYP450 enzymes can be regarded as the main ones responsible for the antineoplasticactivities of the mentioned drugs, respectively. Considering theadvantages of repurposing of drugs with known pharmacology compared tonew drug development studies requiring labor, time and cost, it will beextremely important and valuable to continue the clarification of the differentmechanisms of these antifungals on cancerous cells and benefit from themespecially to increase drug efficacy and overcome drug resistance. In thisreview, the action mechanisms of imidazole antifungals on cancerous cells andconsequently, their potential for use in cancer treatment alone or incombination with conventional therapeutics were discussed in detail.