MDPI - Publisher of Open Access Journals

26 pages, 8885 KB

Open AccessArticle

A Study on the Effect of Quaternization of Polyene Antibiotics’ Structures on Their Activity, Toxicity, and Impact on Membrane Models

by Olga Omelchuk, Anna Tevyashova, Svetlana Efimova, Natalia Grammatikova, Elena Bychkova, George Zatonsky, Lyubov Dezhenkova, Nikita Savin, Svetlana Solovieva, Olga Ostroumova and Andrey Shchekotikhin

Antibiotics 2024, 13(7), 608; https://doi.org/10.3390/antibiotics13070608 - 29 Jun 2024

Cited by 3 | Viewed by 1502

Abstract

Polyene antibiotics have been used in antifungal therapy since the mid-twentieth century. They are highly valued for their broad spectrum of activity and the rarity of pathogen resistance to their action. However, their use in the treatment of systemic mycoses often results in serious side-effects. Recently, there has been a renewed interest in the development of new antifungal drugs based on polyenes, particularly due to the emergence of highly dangerous pathogenic strains of fungi, such as Candida auris, and the increased incidence of mucormycosis. Considerable understanding has been established regarding the structure–biological activity relationships of polyene antifungals. Yet, no previous studies have examined the effect of introducing quaternized fragments into their molecular structure. In this study, we present a series of amides of amphotericin B, nystatin, and natamycin bearing a quaternized group in the side chain, and discuss their biological properties: antifungal activity, cytotoxicity, and effects on lipid bilayers that mimic fungal and mammalian cell membranes. Our research findings suggest that the nature of the introduced quaternized residue plays a more significant role than merely the introduction of a constant positive charge. Among the tested polyenes, derivatives 4b, 5b, and 6b, which contain a fragment of N-methyl-4-(aminomethyl)pyridinium in their structure, are particularly noteworthy due to their biological activity. Full article

(This article belongs to the Section Novel Antimicrobial Agents)

► Show Figures

Figure 1

13 pages, 2310 KB

Open AccessArticle

Physiochemical Characterization of Lipidic Nanoformulations Encapsulating the Antifungal Drug Natamycin

by Luigi Talarico, Ilaria Clemente, Alessandro Gennari, Giulia Gabbricci, Simone Pepi, Gemma Leone, Claudia Bonechi, Claudio Rossi, Simone Luca Mattioli, Nicola Detta and Agnese Magnani

Nanomaterials 2024, 14(8), 726; https://doi.org/10.3390/nano14080726 - 20 Apr 2024

Cited by 3 | Viewed by 2692

Abstract

Natamycin is a tetraene polyene that exploits its antifungal properties by irreversibly binding components of fungal cell walls, blocking the growth of infections. However, topical ocular treatments with natamycin require frequent application due to the low ability of this molecule to permeate the ocular membrane. This limitation has limited the use of natamycin as an antimycotic drug, despite it being one of the most powerful known antimycotic agents. In this work, different lipidic nanoformulations consisting of transethosomes or lipid nanoparticles containing natamycin are proposed as carriers for optical topical administration. Size, stability and zeta potential were characterized via dynamic light scattering, the supramolecular structure was investigated via small- and wide-angle X-ray scattering and 1H-NMR, and the encapsulation efficiencies of the four proposed formulations were determined via HPLC-DAD. Full article

(This article belongs to the Special Issue Advances in Pharmaceutical Applications of Lipid-Based Nanoparticles)

► Show Figures

Figure 1

15 pages, 1836 KB

Open AccessReview

Etiology, Predisposing Factors, Clinical Features and Diagnostic Procedure of Otomycosis: A Literature Review

by Mila Bojanović, Marko Stalević, Valentina Arsić-Arsenijević, Aleksandra Ignjatović, Marina Ranđelović, Milan Golubović, Emilija Živković-Marinkov, Goran Koraćević, Bojana Stamenković and Suzana Otašević

J. Fungi 2023, 9(6), 662; https://doi.org/10.3390/jof9060662 - 13 Jun 2023

Cited by 15 | Viewed by 12109

Abstract

Otomycosis (OM) is a superficial fungal infection of the external auditory canal (EAC) with a worldwide prevalence ranging from 9% to 30%. Commonly, otomycoses are caused by Aspergillus (A.) niger complex and Candida spp. Other causative agents are yeasts of the genera Cryptococcus spp., Rhodotorula spp., Geotrichum candidum, dermatophytes (Trichophyton mentagrophytes), and non-dermatophytes molds (Fusarium spp., Penicillium spp., Mucorales fungi). The widest range of different species causing OM are found in the territories of Iran, India, China, Egypt, Mexico, and Brazil. Fungal infection of the EAC varies from mild to severe forms. It can be acute, subacute, or chronic, and is often unilateral, while the bilateral form is more common in immunocompromised patients. From an epidemiological point of view, tropical and subtropical climates are the most significant risk factor for the development of otomycosis. Other predisposing conditions include clothing habits, EAC hygiene practices, long-term antibiotic therapy, diabetes, and immunodeficiency. Since it is often difficult to distinguish otomycosis from an infection of a different origin, laboratory-based evidence, including standard procedures (microscopy and cultivation), is essential for diagnosis. For the treatment of this superficial fungal infection, there are no official therapeutic guidelines and protocols. However, many antifungals for local application, such as polyene, imidazoles, and allylamines, can be applied, as well as systemic antimycotics (triazoles) in severe forms of infection. Full article

(This article belongs to the Special Issue Hot Topics in Superficial Fungal Infections)

► Show Figures

Figure 1

12 pages, 2440 KB

Open AccessArticle

Insight into the Antifungal Effects of Propolis and Carnosic Acid—Extension to the Pathogenic Yeast Candida glabrata: New Propolis Fractionation and Potential Synergistic Applications

by Alejandra Argüelles, Ruth Sánchez-Fresneda, José P. Guirao-Abad, José Antonio Lozano, Francisco Solano and Juan-Carlos Argüelles

J. Fungi 2023, 9(4), 442; https://doi.org/10.3390/jof9040442 - 4 Apr 2023

Cited by 6 | Viewed by 2819

Abstract

Fungi have traditionally been considered opportunistic pathogens in primary infections caused by virulent bacteria, protozoan, or viruses. Consequently, antimycotic chemotherapy is clearly less developed in comparison to its bacterial counterpart. Currently, the three main families of antifungals (polyenes, echinocandins, and azoles) are not sufficient to control the enormous increase in life-threatening fungal infections recorded in recent decades. Natural substances harvested from plants have traditionally been utilized as a successful alternative. After a wide screening of natural agents, we have recently obtained promising results with distinct formulations of carnosic acid and propolis on the prevalent fungal pathogens Candida albicans and Cryptococcus neoformans. Here, we extended their use to the treatment against the emerging pathogenic yeast Candida glabrata, which displayed lower susceptibility in comparison to the fungi mentioned above. Taking into account the moderate antifungal activity of both natural agents, the antifungal value of these combinations has been improved through the obtention of the hydroethanolic fractions of propolis. In addition, we have demonstrated the potential clinical application of new therapeutical designs based on sequential pre-treatments with carnosic/propolis mixtures, followed by exposure to amphotericin B. This approach increased the toxic effect induced by this polyene. Full article

(This article belongs to the Special Issue Antifungal Discovery of Natural Products)

► Show Figures

Figure 1

13 pages, 467 KB

Open AccessEditor’s ChoiceReview

Antifungal Drug Resistance: An Emergent Health Threat

by Antonio Vitiello, Francesco Ferrara, Mariarosaria Boccellino, Annarita Ponzo, Carla Cimmino, Emilio Comberiati, Andrea Zovi, Salvatore Clemente and Michela Sabbatucci

Biomedicines 2023, 11(4), 1063; https://doi.org/10.3390/biomedicines11041063 - 31 Mar 2023

Cited by 116 | Viewed by 12502

Abstract

Fungal infections, named mycosis, can cause severe invasive and systemic diseases that can even lead to death. In recent years, epidemiological data have recorded an increase in cases of severe fungal infections, caused mainly by a growing number of immunocompromised patients and the emergence of fungal pathogenic forms that are increasingly resistant to antimycotic drug treatments. Consequently, an increase in the incidence of mortality due to fungal infections has also been observed. Among the most drug-resistant fungal forms are those belonging to the Candida and Aspergillus spp. Some pathogens are widespread globally, while others are endemic in some areas only. In addition, some others may represent a health threat for some specific subpopulations and not for the general public. In contrast to the extensive therapeutic armamentarium available for the antimicrobial chemotherapeutic treatment of bacteria, for fungal infections there are only a few classes of antimycotic drugs on the market, such as polyenes, azoles, echinocandins, and a few molecules are under trial. In this review, we focused on the systemic mycosis, highlighted the antifungal drug compounds available in the pipeline, and analyzed the main molecular mechanisms for the development of antifungal resistance to give a comprehensive overview and increase awareness on this growing health threat. Full article

(This article belongs to the Special Issue Antimicrobial Resistance: A Global Challenge)

► Show Figures

Figure 1

16 pages, 257 KB

Open AccessReview

Therapy of Non-Dermatophytic Mycoses in Animals

by Daniel Elad

J. Fungi 2018, 4(4), 120; https://doi.org/10.3390/jof4040120 - 30 Oct 2018

Cited by 13 | Viewed by 5892

Abstract

This review focuses on aspects of antimycotic therapy specific to veterinary medicine. In the first part, drug availability, limited mostly by economic consideration but also by clinical applicability and specific adverse effects, is described for polyenes, 5 fluorocytosine, azoles, echinocandins and terbinafine. In the second part, current knowledge and experience in the treatment of selected fungal infections are overviewed. These mycoses include disseminated mold infections in small animals (dogs and cats) and avian species, upper respiratory tract infections of small animals (sino-nasal and sino-orbital aspergillosis) and horses (guttural pouch mycosis), eumycetoma, infections caused by dimorphic fungi, (blastomycosis, histoplasmosis, coccidioidomycosis, paracoccidioidomycosis and sporothrichosis) and by yeasts and yeast-like microorganism (Cryptococcus spp. and Malassezia pachydermatis). Full article

(This article belongs to the Special Issue Treatments for Fungal Infections)

Search Results (6)

Further Information

Guidelines

MDPI Initiatives

Follow MDPI

Saved Queries

Search Filter Reset All

Years

Feature Papers

Subjects

Journals

Article Types

Countries / Regions

Search Results (6)

Further Information

Guidelines

MDPI Initiatives

Follow MDPI