Antifungal Agents: Pharmacological Mechanisms, Molecular Targets, and Resistance Development

The increase in the number of fungal infections, particularly in individuals with a weak immune system, makes the use of antifungal drugs essential in the treatment process. These medicines act differently in interfering with crucial processes in fungal cells. They are primarily polyenes (binding to ergosterol and raising cell membrane permeability of fungi), azoles (inhibiting ergosterol synthesis), echinocandins (disrupting the cell wall of fungi by inhibiting β-glucan synthesis), and antimetabolites such as flucytosine (disrupting fungal cell and RNA synthesis). Other medications like griseofulvin and terbinafine are aimed at the division or formation of the membrane by the fungus and are selected according to the species and the extent of the infection. The application of these drugs is, however, constrained by side effects, low penetration in some tissues and increasing resistance. The mechanisms by which fungi are resistant to drugs include alteration of the drug target, enhanced drug efflux, metabolic adaptation, and biofilm protection. The genomics, proteomics and molecular biology have enhanced knowledge of the disease pathogenesis and resistance to therapy in fungi and led to the development of new drugs, improved formulations, nanoparticle delivery systems, and cross-therapy.  Though progress has been made, it is not that easy to develop antifungal drugs because fungi are biologically close to humans and it is difficult to find antifungal drugs that do not cause harm to human cells. Continuous investigation on the resistance mechanisms, fungal metabolism and novel approaches to treatment are crucial to enhance the efficacy of the drugs, decrease the toxicity and overcome the resistant fungal infections.