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Antibiotics
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Fungal Metabolites and Synthetic Derivatives: Antimicrobial Properties Toward Microbial Pathogens
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Fungal Metabolites and Synthetic Derivatives: Antimicrobial Properties Toward Microbial Pathogens

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Fungi and Their Metabolites".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 1450

Special Issue Editor

Prof. Dr. João Vicente Braga De Souza

E-Mail Website
Guest Editor
Mycology Laboratory, National Institute for Amazonian Research (INPA), Manaus 69067-375, AM, Brazil
Interests: medical mycology; biotechnology; antifungals; bioechnology

Special Issue Information

Dear Colleagues,

The resistance of bacteria to current antibiotics and the limitations in toxicity of antiparasitic and antifungal medications pose significant challenges to global public health. Fungal metabolites and their synthetic derivatives have long been explored as promising alternatives, with notable successes such as penicillins and cephalosporins. Additionally, key antifungal agents (including griseofulvin and echinocandins) originating from fungal sources highlight the importance of these natural products in antimicrobial therapy. Synthetic derivatives of natural products, such as β-lactams, including carbapenems, are crucial in treating resistant bacterial infections. Furthermore, the development of synthetic triazole derivatives has enhanced antifungal therapy, providing broader-spectrum activity and better pharmacokinetic properties. These compounds exemplify the potential of synthetic modifications to enhance efficacy and reduce toxicity.

This Special Issue aims to explore the antimicrobial properties of fungal metabolites and their synthetic derivatives, focusing on innovative approaches to combat microbial pathogens. We invite contributions that delve into the discovery, development, and application of these compounds, as well as their underlying mechanisms of action.

We encourage researchers worldwide to submit original research articles and reviews related to fungal metabolites and synthetic derivatives. Moreover, this Special Issue is proudly edited by João Vicente Braga de Souza, one of the Amazonian researchers dedicated to exploring the unparalleled fungal biodiversity of the Amazon in search of new antimicrobial agents.

Potential themes include the identification of novel fungal metabolites, synthetic modifications of natural products, and case studies of successful antimicrobial applications. Original research and reviews are welcome.

We look forward to your contributions to this Special Issue, which symbolizes a collective effort to discover the next generation of antibiotics.

Prof. Dr. João Vicente Braga De Souza
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antimicrobial resistance
  • fungal metabolites
  • synthetic derivatives
  • antifungal agents
  • bioactive compounds

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Published Papers (2 papers)

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Research

19 pages, 3813 KiB  
Article
An OSMAC Strategy for the Production of Antimicrobial Compounds by the Amazonian Fungi Talaromyces pinophilus CCM-UEA-F0414 and Penicillium paxilli CCM-UEA-F0591
by Cleudiane Pereira de Andrade, Caroline Dutra Lacerda, Raíssa Assímen Valente, Liss Stone de Holanda Rocha, Anne Terezinha Fernandes de Souza, Dorothy Ívila de Melo Pereira, Larissa Kirsch Barbosa, Cleiton Fantin, Sergio Duvoisin Junior and Patrícia Melchionna Albuquerque
Antibiotics 2025, 14(8), 756; https://doi.org/10.3390/antibiotics14080756 - 27 Jul 2025
Viewed by 267
Abstract
Background/Objectives: The emergence of antimicrobial resistance represents a critical global health threat, requiring the discovery of novel bioactive compounds. Fungi from Amazonian biodiversity are promising sources of secondary metabolites with potential antimicrobial activity. This study aimed to investigate the production of antimicrobial compounds [...] Read more.
Background/Objectives: The emergence of antimicrobial resistance represents a critical global health threat, requiring the discovery of novel bioactive compounds. Fungi from Amazonian biodiversity are promising sources of secondary metabolites with potential antimicrobial activity. This study aimed to investigate the production of antimicrobial compounds by two Amazonian fungal strains using the OSMAC (One Strain–Many Compounds) approach. Methods: Two fungal strains, Talaromyces pinophilus CCM-UEA-F0414 and Penicillium paxilli CCM-UEA-F0591, were cultivated under five distinct culture media to modulate secondary metabolite production. Ethyl acetate extracts were prepared and evaluated for antimicrobial activity against Gram-positive and Gram-negative bacteria, as well as pathogenic yeasts. Chemical characterization was performed using thin-layer chromatography (TLC), Fourier Transform Infrared Spectroscopy (FTIR), Ultraviolet–Visible (UV-Vis) spectroscopy, and Ultra-High-Performance Liquid Chromatography with Diode Array Detection (uHPLC-DAD). Results: The extracts exhibited significant antimicrobial activity, with minimum inhibitory concentrations (MICs) ranging from 78 to 5000 µg/mL. Chemical analyses revealed the presence of phenolic compounds, particularly caffeic and chlorogenic acids. Variations in the culture media substantially affected both the metabolite profiles and antimicrobial efficacy of the extracts. Conclusions: The OSMAC strategy effectively enhanced the metabolic diversity of the Amazonian fungal strains, leading to the production of bioactive metabolites with antimicrobial potential. These findings support the importance of optimizing culture conditions to unlock the biosynthetic capacity of Amazonian fungi as promising sources of antimicrobial agents. Full article
(This article belongs to the Special Issue Fungal Metabolites and Synthetic Derivatives: Antimicrobial Properties Toward Microbial Pathogens)
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15 pages, 1157 KiB  
Article
Antifungal Activity of Selected Naphthoquinones and Their Synergistic Combination with Amphotericin B Against Cryptococcus neoformans H99
by Naira Sulany Oliveira de Sousa, Juan Diego Ribeiro de Almeida, Linnek Silva da Rocha, Izabela de Mesquita Bárcia Moreira, Flávia da Silva Fernandes, Ani Beatriz Jackisch Matsuura, Kátia Santana Cruz, Emersom Silva Lima, Érica Simplício de Souza, Hagen Frickmann and João Vicente Braga de Souza
Antibiotics 2025, 14(6), 602; https://doi.org/10.3390/antibiotics14060602 - 13 Jun 2025
Viewed by 851
Abstract
Background/Objectives: Cryptococcosis, caused by Cryptococcus neoformans and Cryptococcus gattii species complexes, remains a significant health concern, particularly among immunocompromised patients. The emergence of antifungal resistance and toxicity of conventional treatment underscore the urgent need for novel therapeutic approaches. Combination therapies represent a promising [...] Read more.
Background/Objectives: Cryptococcosis, caused by Cryptococcus neoformans and Cryptococcus gattii species complexes, remains a significant health concern, particularly among immunocompromised patients. The emergence of antifungal resistance and toxicity of conventional treatment underscore the urgent need for novel therapeutic approaches. Combination therapies represent a promising strategy to enhance efficacy and overcome resistance. This study investigated the antifungal activity of five naphthoquinones against nine isolates of Cryptococcus spp. and assessed their synergistic effects with amphotericin B (AmB). Methods: In this study, five selected naphthoquinones were evaluated for their antifungal activity against Cryptococcus spp. isolates using broth microdilution assays to determine minimum inhibitory concentrations (MICs), according to CLSI guidelines. The potential synergistic effect with AmB was assessed using checkerboard assays, with synergy interpreted based on the fractional inhibitory concentration index (FICI). Cytotoxicity was evaluated in MRC-5 human lung fibroblast cells using the MTT assay. Results: Among the compounds tested, 2-methoxynaphthalene-1,4-dione (2-MNQ) demonstrated antifungal activity, with MIC values ranging from 3.12 to 12.5 µg/mL. Checkerboard assays revealed a synergistic interaction between 2-MNQ and AmB, with a fractional inhibitory concentration index (FICI) of 0.27. The combination reduced the MIC of AmB by 4.17-fold. These findings highlight the potential of synthetic naphthoquinones, particularly 2-MNQ, as effective antifungal agents with synergistic properties when combined with AmB. The observed synergy suggests complementary mechanisms, including increased fungal membrane permeability and oxidative stress induction. Conclusions: This study highlights the potential of 2-MNQ and 2,3-DBNQ as antifungal candidates against Cryptococcus spp., with emphasis on the synergistic interaction observed between 2-MNQ and amphotericin B. The findings reinforce the importance of structural modifications in naphthoquinones to enhance antifungal activity and support the need for further preclinical studies investigating combination therapies aimed at improving treatment efficacy in patients with cryptococcosis. Full article
(This article belongs to the Special Issue Fungal Metabolites and Synthetic Derivatives: Antimicrobial Properties Toward Microbial Pathogens)
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