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Antifungal Drug Discovery: Progresses, Challenges, Opportunities
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Antifungal Drug Discovery: Progresses, Challenges, Opportunities

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 29 August 2024 | Viewed by 1486

Special Issue Editor

Dr. Bernhard Biersack

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Guest Editor
Organic Chemistry Laboratory, University of Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany
Interests: medicinal chemistry; natural products; multi-component reactions; metal-based drugs; antibiotics and antimycotics; anticancer drugs; antiparasitic drugs; antiviral drugs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The arsenal of antifungal drugs for the treatment of human mycoses is confined to a few compound classes such as azoles, echinocandines and polyenes, while the eminent health risks based on fungal infections are continuously rising. Immunocompromised people (e.g., elderly people, organ transplantation and cancer patients, persons infected with HIV) especially suffer from life-threatening systemic fungal infections. The formation of drug-resistant pathogenic fungal strains, as well as the emergence of new highly problematic species such as Candida auris, pose a considerable global threat, warranting the development of new and efficient antifungal drug candidates with limited side effects. The severe skin mycoses eumycetoma, chromoblastomycosis and sporotrichosis are classified as neglected tropical diseases (NTDs), with potent antifungals still needing to be discovered and existing drugs being inefficient and often unavailable for patients in rural tropical and subtropical regions.

Thus, new fungicidals with enhanced activity, reduced side effects, and the ability to circumvent drug resistance mechanisms are sought. Promising strategies include the optimization of existing antifungals and the development of first-generation inhibitors of new fungal drug targets. In this regard, the identification and validation of suitable new targets and mechanisms is of high relevance, and these can also include vital interactions of the fungal pathogen with the host. Straightforward formulation and conjugate systems can improve pharmacokinetics and targeting properties. The repurposing of known drugs against other ailments and the rapid and cost-effective application of few-step chemical procedures and multi-component reactions can quickly lead to useful hit compounds.

This Special Issue covers the latest developments and the state of the art of drug design and discovery for the treatment of fungal infections. Original research articles, review articles, perspectives and short communications including (but not restricted to) the described research fields are welcome.

Dr. Bernhard Biersack
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • antifungal drugs
  • fungal infections
  • drug design
  • drug discovery
  • targeted therapy
  • drug resistance
  • fungal drug targets
  • neglected tropical diseases

Published Papers (2 papers)

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19 pages, 8343 KiB  
Article
Anti-Biofilm Activity of Assamsaponin A, Theasaponin E1, and Theasaponin E2 against Candida albicans
by Yuhong Chen, Ying Gao, Yifan Li and Junfeng Yin
Int. J. Mol. Sci. 2024, 25(7), 3599; https://doi.org/10.3390/ijms25073599 - 22 Mar 2024
Viewed by 570
Abstract
Biofilm formation plays a crucial role in the pathogenesis of Candida albicans and is significantly associated with resistance to antifungal agents. Tea seed saponins, a class of non-ionic triterpenes, have been proven to have fungicidal effects on planktonic C. albicans. However, their [...] Read more.
Biofilm formation plays a crucial role in the pathogenesis of Candida albicans and is significantly associated with resistance to antifungal agents. Tea seed saponins, a class of non-ionic triterpenes, have been proven to have fungicidal effects on planktonic C. albicans. However, their anti-biofilm activity and mechanism of action against C. albicans remain unclear. In this study, the effects of three Camellia sinensis seed saponin monomers, namely, theasaponin E1 (TE1), theasaponin E2 (TE2), and assamsaponin A (ASA), on the metabolism, biofilm development, and expression of the virulence genes of C. albicans were evaluated. The results of the XTT reduction assay and crystal violet (CV) staining assay demonstrated that tea seed saponin monomers concentration-dependently suppressed the adhesion and biofilm formation of C. albicans and were able to eradicate mature biofilms. The compounds were in the following order in terms of their inhibitory effects: ASA > TE1 > TE2. The mechanisms were associated with reductions in multiple crucial virulence factors, including cell surface hydrophobicity (CSH), adhesion ability, hyphal morphology conversion, and phospholipase activity. It was further demonstrated through qRT-PCR analysis that the anti-biofilm activity of ASA and TE1 against C. albicans was attributed to the inhibition of RAS1 activation, which consequently suppressed the cAMP–PKA and MAPK signaling pathways. Conversely, TE2 appeared to regulate the morphological turnover and hyphal growth of C. albicans via a pathway that was independent of RAS1. These findings suggest that tea seed saponin monomers are promising innovative agents against C. albicans. Full article
(This article belongs to the Special Issue Antifungal Drug Discovery: Progresses, Challenges, Opportunities)
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Review

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16 pages, 962 KiB  
Review
Phytotherapy of Vulvovaginal Candidiasis: A Narrative Review
by Natalia Picheta, Julia Piekarz, Oliwia Burdan, Małgorzata Satora, Rafał Tarkowski and Krzysztof Kułak
Int. J. Mol. Sci. 2024, 25(7), 3796; https://doi.org/10.3390/ijms25073796 - 28 Mar 2024
Viewed by 557
Abstract
Vulvovaginal candidiasis (VVC) is a real gynecological problem among women of reproductive age from 15 to 49. A recent analysis showed that 75% of women will have an occurrence at least once per year, while 5% are observed to have recurrent vaginal mycosis—these [...] Read more.
Vulvovaginal candidiasis (VVC) is a real gynecological problem among women of reproductive age from 15 to 49. A recent analysis showed that 75% of women will have an occurrence at least once per year, while 5% are observed to have recurrent vaginal mycosis—these patients may become unwell four or more times a year. This pathology is caused in 85–90% of cases by fungi of the Candida albicans species. It represents an intractable medical problem for female patients due to pain and pruritus. Due to the observation of an increasing number of strains resistant to standard preparations and an increase in the recurrence of this pathology when using local or oral preferential therapy, such as fluconazole, an analysis was launched to develop alternative methods of treating VVC using herbs such as dill, turmeric, and berberine. An in-depth analysis of databases that include scientific articles from recent years made it possible to draw satisfactory conclusions supporting the validity of herbal therapy for the pathology in question. Although phytotherapy has not yet been approved by the Food and Drug Administration, it appears to be a promising therapeutic solution for strains that are resistant to existing treatments. There is research currently undergoing aimed at comparing classical pharmacotherapy and herbal therapy in the treatment of vaginal candidiasis for the purpose of increasing medical competence and knowledge for the care of the health and long-term comfort of gynecological patients. Full article
(This article belongs to the Special Issue Antifungal Drug Discovery: Progresses, Challenges, Opportunities)
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