Imidazole Antifungals: A Review of Their Action Mechanisms on Cancerous Cells

Imidazoles, together with triazoles, constitute azole sub-group of antifungal drugs which acts by inhibiting cytochrome P450-dependent enzyme, the lanosterol 14-α-demethylase. In addition to their primary use, when it comes to additional anti-cancer function, clotrimazole, econazole and ketoconazole have come to the fore among the imidazoles. Based on the findings up to now, although having different effects, disruption of the glycolytic pathway, blockage of Ca2+ influx and nonspecific inhibition of CYP450 enzymes can be regarded as the main ones responsible for the anti-neoplastic activities of the mentioned drugs, respectively. Considering the advantages of repurposing of drugs with known pharmacology compared to new drug development studies requiring labor, time and cost, it will be extremely important and valuable to continue the clarification of the different mechanisms of these antifungals on cancerous cells and benefit from them especially to increase drug efficacy and overcome drug resistance. In this review, the action mechanisms of imidazole antifungals on cancerous cells and consequently, their potential for use in cancer treatment alone or in combination with conventional therapeutics were discussed in detail. Imidazoles, together with triazoles, constitute azole sub-group of antifungal drugs which acts by inhibiting cytochrome P450-dependent enzyme, the lanosterol 14-α-demethylase. In addition to their primary use, when it comes to additional anti-cancer function, clotrimazole, econazole and ketoconazole have come to the fore among the imidazoles. Based on the findings up to now, although having different effects, disruption of the glycolytic pathway, blockage of Ca2+ influx and nonspecific inhibition of CYP450 enzymes can be regarded as the main ones responsible for the anti-neoplastic activities of the mentioned drugs, respectively. Considering the advantages of repurposing of drugs with known pharmacology compared to new drug development studies requiring labor, time and cost, it will be extremely important and valuable to continue the clarification of the different mechanisms of these antifungals on cancerous cells and benefit from them especially to increase drug efficacy and overcome drug resistance. In this review, the action mechanisms of imidazole antifungals on cancerous cells and consequently, their potential for use in cancer treatment alone or in combination with conventional therapeutics were discussed in detail.