Synergy between azoles and 1,4-dihydropyridine derivative as an option to control fungal infections

With emerging fungal infections and developing resistance, there is a need for understanding the mechanisms of resistance as well as its clinical impact while planning the treatment strategies. Several approaches could be taken to overcome the problems arising from the management of fungal diseases. Besides the discovery of novel effective agents, one realistic alternative is to enhance the activity of existing agents. This strategy could be achieved by combining existing antifungal agents with other bioactive substances with known activity profiles (combination therapy). Azole antifungals are the most frequently used class of substances used to treat fungal infections. Fluconazole is often the first choice for antifungal treatment. The aim of this work was to study potential synergy between azoles and 1,4-dihydropyridine-2,3,5-tricarboxylate (termed derivative H) in order to control fungal infections. This article points out the synergy between azoles and newly synthesized derivative H in order to fight fungal infections. Experiments confirmed the role of derivative H as substrate/inhibitor of fungal transporter Cdr1p relating to increased sensitivity to fluconazole. These findings, plus decreased expression of ERG11, are responsible for the synergistic effect.