Novel Approaches for Efficient Antifungal Drug Action

Abstract

The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases that further threaten health, especially in immunodeficient populations, is a major global problem. The development of new antifungal agents in clinical trials is inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms aim at certain characteristics of the fungus in order to avoid biological similarities with the host. Synthesis of the cell wall and ergosterol are mainly targeted in clinical use. The need for new approaches to antifungal therapeutic agents or development alternatives has increased. This review explores new perspectives on mechanisms to effectively combat fungal infections and effective antifungal activity. The clinical drug have a common feature that ultimately causes caspase-dependent cell death. The drugs-induced cell death pathway is associated with mitochondrial dysfunction, including mitochondrial membrane depolarization and cytochrome c release. This mechanism of action also reveals antimicrobial peptides, the primary effector molecules of innate systems, to highlight new alternatives. Furthermore, drug combination therapy is suggested as another strategy to combat fungal infection. The proposal for a new approach to antifungal agents is not only important from a basic scientific point of view, but will also assist in the selection of molecules for combination therapy.

Rondonin: antimicrobial properties and mechanism of action

“…echinocandins [15][16][17]. Although these drugs target a marked fungal pathway, there is an urgent need to develop new antifungal agents that are more effective, fungalspecific, have no or reduced toxicity, and simultaneously do not cause resistance [18].…”

“…The number of antifungals currently available for clinicians is limited, and the scenario is worsened by the rise of antifungal resistance to available drugs such as azoles, polyenes, and echinocandins [15][16][17]. Although these drugs target a marked fungal pathway, there is an urgent need to develop new antifungal agents that are more effective, are fungal-specific, have no or reduced toxicity, and simultaneously do not cause resistance [18].…”

Nanoparticles as a Tool for Broadening Antifungal Activities

“…The major problems for the individual who needs this type of treatment are the side effects. Although the fungal cell exhibits some differences to the animal cell, such as the composition of its membrane and cell wall, the similarity between both is still large, which limits specific antifungal sites of action and increases the likelihood of toxicity [163,78].…”

Synthesis and antifungal activity of new O-alkylamidoximes

“…Currently, there is a major concern about the growing cases of microbial resistance worldwide, since, in the absence of efficient antimicrobial agents, it is estimated that incurable diseases will be responsible for about 10 million casualties by 2050 (De Kraker et al 2016). Thus, the continuous prospection for molecules that may be useful in the development of new therapeutic agents is a highly relevant issue and has been encouraged, mainly due to the appearance of new drugs on the market not to follow the appearance of new resistant microorganisms (Pfaller 2012;Lee and Lee 2018).…”