Undeniably, new antifungal treatments are necessary against pathogenic fungi. Fungal infections have significantly increased in recent decades, being highlighted as important causes of morbidity and mortality, particularly in immunocompromised patients. Five main antifungal classes are used: (i) azoles, (ii) echinocandins, (iii) polyenes, (iv) allylamines and (v) pyrimidine analogues. Moreover, the treatment of mycoses has several limitations, such as undesirable side effects, narrow activity spectrum, a small number of targets and fungal resistance, which are still of major concern in clinical practice. The discovery of new antifungals is mostly achieved by the screening of natural or synthetic/semisynthetic chemical compounds. The most recent discoveries in drug resistance mechanism and their avoidance were explored in a review, focusing on different antifungal targets, as well as new agents or strategies, such as combination therapy, that could improve antifungal therapy.

Significance and Impact of the Study
The failure to respond to antifungal therapy is complex and is associated with microbiological resistance and increased expression of virulence in fungal pathogens. Thus, this review offers an overview of current challenges in the treatment of fungal infections associated with increased antifungal drug resistance and the formation of biofilms in these opportunistic pathogens. Furthermore, the most recent and potential strategies to combat fungal pathogens are explored here, focusing on new agents as well as innovative approaches, such as combination therapy between antifungal drugs or with natural compounds.

Antifungals discovery: an insight into new strategies to combat antifungal resistance

Geraniol presents many pharmacological properties including antifungal and antibacterial activity. The objective of this study was to conduct a review of the literature concerning in vitro antimicr...

Antimicrobial activity of geraniol: an integrative review

Dermatomycosis causes highly frequent dermal lesions, and volatile oils have been proven to be promising as antifungal agents. The antifungal activity of geraniol, nerol, citral, neral and geranial (monoterpenes), and terbinafine and anidulafungin (control drugs) against seven opportunistic pathogenic yeasts and four dermatophyte species was evaluated by the Clinical and Laboratory Standards Institute microdilution tests. Monoterpenes were more active against dermatophytes than yeasts (geometric mean of minimal inhibitory concentration (GMIC) of 34.5 and 100.4 µg.ml-1, respectively). Trichophyton rubrum was the fungal species most sensitive to monoterpenes (GMIC of 22.9 µg.ml-1). The trans isomers showed higher antifungal activity than the cis. The mechanism of action was investigated evaluating damage in the fungal cell wall (Sorbitol Protection Assay) and in the cell membrane (Ergosterol Affinity Assay). No changes were observed in the MIC of monoterpenes in the sorbitol protection assay.The MIC of citral and geraniol was increased from 32 to 160 µg.ml-1 when the exogenous ergosterol concentrations was zero and 250 µg.ml-1, respectively. The monoterpenes showed an affinity for ergosterol relating their mechanism of action to cell membrane destabilization.

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Antifungal activity and mechanism of action of monoterpenes against dermatophytes and yeasts

The increased incidence of fungal infections, associated with the widespread use of antifungal drugs, has resulted in the development of resistance, making it necessary to discover new therapeutic alternatives. Among fungal infections, dermatophytoses constitute a serious public health problem, affecting 20–25 % of the world population. Medicinal plants represent an endless source of bioactive molecules, and their volatile and non-volatile extracts are clearly recognized for being the historical basis of therapeutic health care. Because of this, the research on natural products with antifungal activity against dermatophytes has considerably increased in recent years. However, despite the recognized anti-dermatophytic potential of natural products, often advantageous face to commercial drugs, there is still a long way to go until their use in therapeutics. This review attempts to summarize the current status of anti-dermatophytic natural products, focusing on their mechanism of action, the developed pharmaceutical formulations and their effectiveness in human and animal models of infection.

Natural Products: An Alternative to Conventional Therapy for Dermatophytosis?

Ou-gon, an extract from Scutellaria baicalensis Georgi root, has been shown to exhibit pronounced antifungal activity. The present study aimed to identify antifungal components of Ou-gon and to determine their mechanism of action against pathogenic fungi. Antifungal activity was assessed by the microbroth dilution method using four common human pathogenic fungi, Trichophyton rubrum, Trichophyton mentagrophytes, Aspergillus fumigatus, and Candida albicans. Components of crude Ou-gon extract were separated by reversed-phase high-performance liquid chromatography. Active antifungal components were identified by liquid chromatography-electrospray ionization tandem mass spectrometry. Terminal deoxynucleotidyl transferase dUTP nick end-labelling assay, SYTOX® green uptake assay, determination of intracellular reactive oxygen species and mitochondrial membrane potential as well as microscopy (confocal laser microscopy, scanning and transmission electron microscopy) were used to probe the mode of action. Two components with potent antifungal activity, baicalein and wogonin, were identified in Ou-gon. Baicalein showed potent antifungal activity against the four fungi tested. Wogonin displayed antifungal activity against all four fungi except C. albicans. The components are considered to induce apoptosis-like programmed cell death via hyperproduction of reactive oxygen species. This study enhances our understanding of the antifungal activity of Kampo medicine, and may contribute to the development of new and safe antifungal therapeutics.

/pdf/antifungal-activity-and-mechanism-of-action-of-ou-gon-4lw04xc2w6.pdf

Antifungal activity and mechanism of action of Ou-gon (Scutellaria root extract) components against pathogenic fungi.

This article describes the development and optimiza tion of a UV spectrophotometric method to evaluate the isomers of citral in cyclodextrins complexes by a p artial least squares (PLS) regression model. The ce ntral composite de- sign (CCD) associated with the response surface met hodology (RSM) was applied to select the wavelength range that provides the best prediction results. -cyclodextrin ( -CD) and hydroxypropyl- -cyclodextrin (HP- -CD) complexes with citral were prepared in ethanolic solution and spra y dried. These samples were analyzed by an optimize d PLS-UV model and the results compared with HPLC-UV determination s to evaluate the predictive power of the PLS-UV mo del. The re- sults from the PLS-UV model showed a relative stand ard deviation of prediction (RSEP) ranging from 0.8

Fernanda Battisti

Papers

Antifungal activity and mechanism of action of monoterpenes against dermatophytes and yeasts

Spectrophotometric Simultaneous Determination of Citral Isomers in Cyclodextrin Complexes with Partial Least Squares Supported Approach