Editorial

7 pages, 246 KiB

Open AccessEditorial

Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing

by Jong H. Kim, Luisa W. Cheng and Kirkwood M. Land

Pharmaceuticals 2022, 15(7), 787; https://doi.org/10.3390/ph15070787 - 24 Jun 2022

Cited by 4 | Viewed by 2140

This Special Issue of Pharmaceuticals describes recent advances accomplished in the field of antifungal development, especially the discovery of new drugs and drug repurposing [...] Full article

(This article belongs to the Special Issue Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing)

Research

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14 pages, 986 KiB

Open AccessArticle

Synthetic Derivatives against Wild-Type and Non-Wild-Type Sporothrix brasiliensis: In Vitro and In Silico Analyses

by Lais Cavalcanti dos Santos Velasco de Souza, Lucas Martins Alcântara, Pãmella Antunes de Macêdo-Sales, Nathália Faria Reis, Débora Sena de Oliveira, Ricardo Luiz Dantas Machado, Reinaldo Barros Geraldo, André Luis Souza dos Santos, Vítor Francisco Ferreira, Daniel Tadeu Gomes Gonzaga, Fernando de Carvalho da Silva, Helena Carla Castro and Andréa Regina de Souza Baptista

Pharmaceuticals 2022, 15(1), 55; https://doi.org/10.3390/ph15010055 - 01 Jan 2022

Cited by 6 | Viewed by 1829

Abstract

Recently, the well-known geographically wide distribution of sporotrichosis in Brazil, combined with the difficulties of effective domestic feline treatment, has emphasized the pressing need for new therapeutic alternatives. This work considers a range of synthetic derivatives as potential antifungals against Sporothrix brasiliensis isolated [...] Read more.

Recently, the well-known geographically wide distribution of sporotrichosis in Brazil, combined with the difficulties of effective domestic feline treatment, has emphasized the pressing need for new therapeutic alternatives. This work considers a range of synthetic derivatives as potential antifungals against Sporothrix brasiliensis isolated from cats from the hyperendemic Brazilian region. Six S. brasiliensis isolates from the sporotrichotic lesions of itraconazole responsive or non-responsive domestic cats were studied. The minimum inhibitory concentrations (MICs) of three novel hydrazone derivatives and eleven novel quinone derivatives were determined using the broth microdilution method (M38-A2). In silico tests were also used to predict the pharmacological profile and toxicity parameters of these synthetic derivatives. MICs and MFCs ranged from 1 to >128 µg/mL. The ADMET computational analysis failed to detect toxicity while a good pharmacological predictive profile, with parameters similar to itraconazole, was obtained. Three hydrazone derivatives were particularly promising candidates as antifungal agents against itraconazole-resistant S. brasiliensis from the Brazilian hyperendemic region. Since sporotrichosis is a neglected zoonosis currently spreading in Latin America, particularly in Brazil, the present data can contribute to its future control by alternative antifungal drug design against S. brasiliensis, the most virulent and prevalent species of the hyperendemic context. Full article

(This article belongs to the Special Issue Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing)

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17 pages, 11582 KiB

Open AccessArticle

Echinocandin Drugs Induce Differential Effects in Cytokinesis Progression and Cell Integrity

by Natalia Yagüe, Laura Gómez-Delgado, M. Ángeles Curto, Vanessa S. D. Carvalho, M. Belén Moreno, Pilar Pérez, Juan Carlos Ribas and Juan Carlos G. Cortés

Pharmaceuticals 2021, 14(12), 1332; https://doi.org/10.3390/ph14121332 - 20 Dec 2021

Cited by 3 | Viewed by 2999

Abstract

Fission yeast contains three essential β(1,3)-D-glucan synthases (GSs), Bgs1, Bgs3, and Bgs4, with non-overlapping roles in cell integrity and morphogenesis. Only the bgs4⁺ mutants pbr1-8 and pbr1-6 exhibit resistance to GS inhibitors, even in the presence of the wild-type (WT) sequences of [...] Read more.

Fission yeast contains three essential β(1,3)-D-glucan synthases (GSs), Bgs1, Bgs3, and Bgs4, with non-overlapping roles in cell integrity and morphogenesis. Only the bgs4⁺ mutants pbr1-8 and pbr1-6 exhibit resistance to GS inhibitors, even in the presence of the wild-type (WT) sequences of bgs1⁺ and bgs3⁺. Thus, Bgs1 and Bgs3 functions seem to be unaffected by those GS inhibitors. To learn more about echinocandins’ mechanism of action and resistance, cytokinesis progression and cell death were examined by time-lapse fluorescence microscopy in WT and pbr1-8 cells at the start of treatment with sublethal and lethal concentrations of anidulafungin, caspofungin, and micafungin. In WT, sublethal concentrations of the three drugs caused abundant cell death that was either suppressed (anidulafungin and micafungin) or greatly reduced (caspofungin) in pbr1-8 cells. Interestingly, the lethal concentrations induced differential phenotypes depending on the echinocandin used. Anidulafungin and caspofungin were mostly fungistatic, heavily impairing cytokinesis progression in both WT and pbr1-8. As with sublethal concentrations, lethal concentrations of micafungin were primarily fungicidal in WT cells, causing cell lysis without impairing cytokinesis. The lytic phenotype was suppressed again in pbr1-8 cells. Our results suggest that micafungin always exerts its fungicidal effect by solely inhibiting Bgs4. In contrast, lethal concentrations of anidulafungin and caspofungin cause an early cytokinesis arrest, probably by the combined inhibition of several GSs. Full article

(This article belongs to the Special Issue Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing)

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9 pages, 2573 KiB

Open AccessArticle

Evaluation of Amebicidal and Cysticidal Activities of Antifungal Drug Isavuconazonium Sulfate against Acanthamoeba T4 Strains

by Brian Shing, Mina Balen and Anjan Debnath

Pharmaceuticals 2021, 14(12), 1294; https://doi.org/10.3390/ph14121294 - 11 Dec 2021

Cited by 7 | Viewed by 2276

Abstract

Acanthamoeba species of amebae are often associated with Acanthamoeba keratitis, a severe corneal infection. Isavuconazonium sulfate is an FDA-approved drug for the treatment of invasive aspergillosis and mucormycosis. This prodrug is metabolized into the active isavuconazole moiety. Isavuconazole was previously identified to have [...] Read more.

Acanthamoeba species of amebae are often associated with Acanthamoeba keratitis, a severe corneal infection. Isavuconazonium sulfate is an FDA-approved drug for the treatment of invasive aspergillosis and mucormycosis. This prodrug is metabolized into the active isavuconazole moiety. Isavuconazole was previously identified to have amebicidal and cysticidal activity against Acanthamoeba T4 strains, but the activity of its prodrug, isavuconazonium sulfate, against trophozoites and cysts remains unknown. Since it is not known if isavuconazonium can be metabolized into isavuconazole in the human eye, we evaluated the activities of isavuconazonium sulfate against trophozoites and cysts of three T4 genotype strains of Acanthamoeba. Isavuconazonium displayed amebicidal activity at nanomolar concentrations as low as 1.4 nM and prevented excystation of cysts at concentrations as low as 136 μM. We also investigated the cysticidal activity of isavuconazonium sulfate in combination with a currently used amebicidal drug polyhexamethylene biguanide (PHMB). Although combination of isavuconazonium with PHMB did not elicit an obvious synergistic cysticidal activity, the combination did not cause an antagonistic effect on the cysts of Acanthamoeba T4 strains. Collectively, these findings suggest isavuconazonium retains potency against Acanthamoeba T4 strains and could be adapted for Acanthamoeba keratitis treatment. Full article

(This article belongs to the Special Issue Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing)

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16 pages, 3730 KiB

Open AccessArticle

Synthesis and Study of Antifungal Properties of New Cationic Beta-Glucan Derivatives

by Kamil Kaminski, Magdalena Skora, Paweł Krzyściak, Sylwia Stączek, Agnieszka Zdybicka-Barabas and Małgorzata Cytryńska

Pharmaceuticals 2021, 14(9), 838; https://doi.org/10.3390/ph14090838 - 24 Aug 2021

Cited by 7 | Viewed by 2815

Abstract

The interaction of positively charged polymers (polycations) with a biological membrane is considered to be the cause of the frequently observed toxicity of these macromolecules. If it is possible to obtain polymers with a predominantly negative effect on bacterial and fungal cells, such [...] Read more.

The interaction of positively charged polymers (polycations) with a biological membrane is considered to be the cause of the frequently observed toxicity of these macromolecules. If it is possible to obtain polymers with a predominantly negative effect on bacterial and fungal cells, such systems would have great potential in the treatment of infectious diseases, especially now when reports indicate the growing risk of fungal co-infections in COVID-19 patients. We describe in this article cationic derivatives of natural beta-glucan polymers obtained by reacting the polysaccharide isolated from Saccharomyces boulardii (SB) and Cetraria islandica (CI) with glycidyl trimethyl ammonium chloride (GTMAC). Two synthesis strategies were applied to optimize the product yield. Fungal diseases particularly affect low-income countries, hence the emphasis on the simplicity of the synthesis of such drugs so they can be produced without outside help. The three structures obtained showed selective anti-mycotic properties (against, i.e., Scopulariopsis brevicaulis, Aspergillus brasiliensis, and Fusarium solani), and their toxicity established using fibroblast 3T3-L1 cell line was negligible in a wide range of concentrations. For one of the polymers (SB derivative), using in vivo model of Aspergillus brasiliensis infection in Galleria mellonella insect model, we confirmed the promising results obtained in the preliminary study. Full article

(This article belongs to the Special Issue Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing)

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17 pages, 5542 KiB

Open AccessArticle

The Repurposing of Acetylsalicylic Acid as a Photosensitiser to Inactivate the Growth of Cryptococcal Cells

by Adepemi O. Ogundeji, Nozethu Mjokane, Olufemi S. Folorunso, Carolina H. Pohl, Martin M. Nyaga and Olihile M. Sebolai

Pharmaceuticals 2021, 14(5), 404; https://doi.org/10.3390/ph14050404 - 23 Apr 2021

Cited by 3 | Viewed by 2045

Abstract

Photodynamic treatment (PDT) is often successful when used against aerobic microbes, given their natural susceptibility to oxidative damage. To this end, the current study aimed to explore the photodynamic action of acetylsalicylic acid (ASA; aspirin, which is commonly used to treat non-infectious ailments), [...] Read more.

Photodynamic treatment (PDT) is often successful when used against aerobic microbes, given their natural susceptibility to oxidative damage. To this end, the current study aimed to explore the photodynamic action of acetylsalicylic acid (ASA; aspirin, which is commonly used to treat non-infectious ailments), when administered to respiring cryptococcal cells. The treatment of cryptococcal cells, i.e., exposure to 0.5 or 1 mM of ASA in the presence of ultraviolet light (UVL) for 10 min, resulted in a significant (p < 0.05) reduction in the growth of tested cells when compared to non-treated (non-Rx) cells, i.e., no ASA and no UVL. The treated cells were also characterised by diseased mitochondria, which is crucial for the survival of respiring cells, as observed by a significant (p < 0.05) loss of mitochondrial membrane potential (ΔΨM) and significant (p < 0.05) accumulation of reactive oxygen species (ROS) when compared to non-Rx cells. Moreover, the photolytic products of acetylsalicylic acid altered the ultrastructural appearance of treated cells as well as limited the expression levels of the capsular-associated gene, CAP64, when compared to non-Rx cells. The results of the study highlight the potential use of ASA as a photosensitiser that is effective for controlling the growth of cryptococcal cells. Potentially, this treatment can also be used as an adjuvant, to complement and support the usage of current anti-microbial agents. Full article

(This article belongs to the Special Issue Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing)

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19 pages, 1451 KiB

Open AccessArticle

Design, Synthesis and Anticandidal Evaluation of Indazole and Pyrazole Derivatives

by Karen Rodríguez-Villar, Alicia Hernández-Campos, Lilián Yépez-Mulia, Teresita del Rosario Sainz-Espuñes, Olivia Soria-Arteche, Juan Francisco Palacios-Espinosa, Francisco Cortés-Benítez, Martha Leyte-Lugo, Bárbara Varela-Petrissans, Edgar A. Quintana-Salazar and Jaime Pérez-Villanueva

Pharmaceuticals 2021, 14(3), 176; https://doi.org/10.3390/ph14030176 - 24 Feb 2021

Cited by 11 | Viewed by 2490

Abstract

Candidiasis, caused by yeasts of the genus Candida, is the second cause of superficial and mucosal infections and the fourth cause of bloodstream infections. Although some antifungal drugs to treat candidiasis are available, resistant strains to current therapies are emerging. Therefore, the search [...] Read more.

Candidiasis, caused by yeasts of the genus Candida, is the second cause of superficial and mucosal infections and the fourth cause of bloodstream infections. Although some antifungal drugs to treat candidiasis are available, resistant strains to current therapies are emerging. Therefore, the search for new candicidal compounds is certainly a priority. In this regard, a series of indazole and pyrazole derivatives were designed in this work, employing bioisosteric replacement, homologation, and molecular simplification as new anticandidal agents. Compounds were synthesized and evaluated against C. albicans, C. glabrata, and C. tropicalis strains. The series of 3-phenyl-1H-indazole moiety (10a–i) demonstrated to have the best broad anticandidal activity. Particularly, compound 10g, with N,N-diethylcarboxamide substituent, was the most active against C. albicans and both miconazole susceptible and resistant C. glabrata species. Therefore, the 3-phenyl-1H-indazole scaffold represents an opportunity for the development of new anticandidal agents with a new chemotype. Full article

(This article belongs to the Special Issue Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing)

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Review

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34 pages, 2325 KiB

Open AccessReview

Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox

by Aidan Kane and Dee A. Carter

Pharmaceuticals 2022, 15(4), 482; https://doi.org/10.3390/ph15040482 - 14 Apr 2022

Cited by 15 | Viewed by 5829

Abstract

Fungal infections impact the lives of at least 12 million people every year, killing over 1.5 million. Wide-spread use of fungicides and prophylactic antifungal therapy have driven resistance in many serious fungal pathogens, and there is an urgent need to expand the current [...] Read more.

Fungal infections impact the lives of at least 12 million people every year, killing over 1.5 million. Wide-spread use of fungicides and prophylactic antifungal therapy have driven resistance in many serious fungal pathogens, and there is an urgent need to expand the current antifungal arsenal. Recent research has focused on improving azoles, our most successful class of antifungals, by looking for synergistic interactions with secondary compounds. Synergists can co-operate with azoles by targeting steps in related pathways, or they may act on mechanisms related to resistance such as active efflux or on totally disparate pathways or processes. A variety of sources of potential synergists have been explored, including pre-existing antimicrobials, pharmaceuticals approved for other uses, bioactive natural compounds and phytochemicals, and novel synthetic compounds. Synergy can successfully widen the antifungal spectrum, decrease inhibitory dosages, reduce toxicity, and prevent the development of resistance. This review highlights the diversity of mechanisms that have been exploited for the purposes of azole synergy and demonstrates that synergy remains a promising approach for meeting the urgent need for novel antifungal strategies. Full article

(This article belongs to the Special Issue Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing)

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15 pages, 878 KiB

Open AccessReview

Repurposing Antifungals for Host-Directed Antiviral Therapy?

by Sebastian Schloer, Jonas Goretzko and Ursula Rescher

Pharmaceuticals 2022, 15(2), 212; https://doi.org/10.3390/ph15020212 - 10 Feb 2022

Cited by 7 | Viewed by 2538

Abstract

Because of their epidemic and pandemic potential, emerging viruses are a major threat to global healthcare systems. While vaccination is in general a straightforward approach to prevent viral infections, immunization can also cause escape mutants that hide from immune cell and antibody detection. [...] Read more.

Because of their epidemic and pandemic potential, emerging viruses are a major threat to global healthcare systems. While vaccination is in general a straightforward approach to prevent viral infections, immunization can also cause escape mutants that hide from immune cell and antibody detection. Thus, other approaches than immunization are critical for the management and control of viral infections. Viruses are prone to mutations leading to the rapid emergence of resistant strains upon treatment with direct antivirals. In contrast to the direct interference with pathogen components, host-directed therapies aim to target host factors that are essential for the pathogenic replication cycle or to improve the host defense mechanisms, thus circumventing resistance. These relatively new approaches are often based on the repurposing of drugs which are already licensed for the treatment of other unrelated diseases. Here, we summarize what is known about the mechanisms and modes of action for a potential use of antifungals as repurposed host-directed anti-infectives for the therapeutic intervention to control viral infections. Full article

(This article belongs to the Special Issue Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing)

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21 pages, 3739 KiB

Open AccessEditor’s ChoiceReview

Advances in Antifungal Drug Development: An Up-To-Date Mini Review

by Ghada Bouz and Martin Doležal

Pharmaceuticals 2021, 14(12), 1312; https://doi.org/10.3390/ph14121312 - 16 Dec 2021

Cited by 48 | Viewed by 6783

Abstract

The utility of clinically available antifungals is limited by their narrow spectrum of activity, high toxicity, and emerging resistance. Antifungal drug discovery has always been a challenging area, since fungi and their human host are eukaryotes, making it difficult to identify unique targets [...] Read more.

The utility of clinically available antifungals is limited by their narrow spectrum of activity, high toxicity, and emerging resistance. Antifungal drug discovery has always been a challenging area, since fungi and their human host are eukaryotes, making it difficult to identify unique targets for antifungals. Novel antifungals in clinical development include first-in-class agents, new structures for an established target, and formulation modifications to marketed antifungals, in addition to repurposed agents. Membrane interacting peptides and aromatherapy are gaining increased attention in the field. Immunotherapy is another promising treatment option, with antifungal antibodies advancing into clinical trials. Novel targets for antifungal therapy are also being discovered, allowing the design of new promising agents that may overcome the resistance issue. In this mini review, we will summarize the current status of antifungal drug pipelines in clinical stages, and the most recent advancements in preclinical antifungal drug development, with special focus on their chemistry. Full article

(This article belongs to the Special Issue Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing)

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19 pages, 974 KiB

Open AccessReview

Retinoids in Fungal Infections: From Bench to Bedside

by Terenzio Cosio, Roberta Gaziano, Guendalina Zuccari, Gaetana Costanza, Sandro Grelli, Paolo Di Francesco, Luca Bianchi and Elena Campione

Pharmaceuticals 2021, 14(10), 962; https://doi.org/10.3390/ph14100962 - 24 Sep 2021

Cited by 26 | Viewed by 8896

Abstract

Retinoids—a class of chemical compounds derived from vitamin A or chemically related to it—are used especially in dermatology, oncohematology and infectious diseases. It has been shown that retinoids—from their first generation—exert a potent antimicrobial activity against a wide range of pathogens, including bacteria, [...] Read more.

Retinoids—a class of chemical compounds derived from vitamin A or chemically related to it—are used especially in dermatology, oncohematology and infectious diseases. It has been shown that retinoids—from their first generation—exert a potent antimicrobial activity against a wide range of pathogens, including bacteria, fungi and viruses. In this review, we summarize current evidence on retinoids’ efficacy as antifungal agents. Studies were identified by searching electronic databases (MEDLINE, EMBASE, PubMed, Cochrane, Trials.gov) and reference lists of respective articles from 1946 to today. Only articles published in the English language were included. A total of thirty-nine articles were found according to the criteria. In this regard, to date, In vitro and In vivo studies have demonstrated the efficacy of retinoids against a broad-spectrum of human opportunistic fungal pathogens, including yeast fungi that normally colonize the skin and mucosal surfaces of humans such as Candida spp., Rhodotorula mucilaginosa and Malassezia furfur, as well as environmental moulds such as Aspergillus spp., Fonsecae monofora and many species of dermatophytes associated with fungal infections both in humans and animals. Notwithstanding a lack of double-blind clinical trials, the efficacy, tolerability and safety profile of retinoids have been demonstrated against localized and systemic fungal infections. Full article

(This article belongs to the Special Issue Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing)

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20 pages, 1274 KiB

Open AccessReview

Drug Repurposing in Medical Mycology: Identification of Compounds as Potential Antifungals to Overcome the Emergence of Multidrug-Resistant Fungi

by Lucie Peyclit, Hanane Yousfi, Jean-Marc Rolain and Fadi Bittar

Pharmaceuticals 2021, 14(5), 488; https://doi.org/10.3390/ph14050488 - 20 May 2021

Cited by 25 | Viewed by 4743

Abstract

Immunodepression, whether due to HIV infection or organ transplantation, has increased human vulnerability to fungal infections. These conditions have created an optimal environment for the emergence of opportunistic infections, which is concomitant to the increase in antifungal resistance. The use of conventional antifungal [...] Read more.

Immunodepression, whether due to HIV infection or organ transplantation, has increased human vulnerability to fungal infections. These conditions have created an optimal environment for the emergence of opportunistic infections, which is concomitant to the increase in antifungal resistance. The use of conventional antifungal drugs as azoles and polyenes can lead to clinical failure, particularly in immunocompromised individuals. Difficulties related to treating fungal infections combined with the time required to develop new drugs, require urgent consideration of other therapeutic alternatives. Drug repurposing is one of the most promising and rapid solutions that the scientific and medical community can turn to, with low costs and safety advantages. To treat life-threatening resistant fungal infections, drug repurposing has led to the consideration of well-known and potential molecules as a last-line therapy. The aim of this review is to provide a summary of current antifungal compounds and their main resistance mechanisms, following by an overview of the antifungal activity of non-traditional antimicrobial drugs. We provide their eventual mechanisms of action and the synergistic combinations that improve the activity of current antifungal treatments. Finally, we discuss drug repurposing for the main emerging multidrug resistant (MDR) fungus, including the Candida auris, Aspergillus or Cryptococcus species. Full article

(This article belongs to the Special Issue Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing)

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23 pages, 321 KiB

Open AccessReview

Clotrimazole for Vulvovaginal Candidosis: More Than 45 Years of Clinical Experience

by Werner Mendling, Maged Atef El Shazly and Lei Zhang

Pharmaceuticals 2020, 13(10), 274; https://doi.org/10.3390/ph13100274 - 25 Sep 2020

Cited by 18 | Viewed by 7112

Abstract

Vulvovaginal candidosis is a common disease, and various treatment strategies have emerged over the last few decades. Clotrimazole belongs to the drugs of choice for the treatment of vulvovaginal candidosis. Although available for almost 50 years, systematic reviews on the usefulness of topical [...] Read more.

Vulvovaginal candidosis is a common disease, and various treatment strategies have emerged over the last few decades. Clotrimazole belongs to the drugs of choice for the treatment of vulvovaginal candidosis. Although available for almost 50 years, systematic reviews on the usefulness of topical clotrimazole across disease severity and populations affected are scarce. Thus, we conducted a systematic literature search in the PubMed and Embase databases to summarize the effectiveness and safety of topical clotrimazole in the treatment of uncomplicated (acute) and complicated vulvovaginal candidosis. In total, 37 randomized controlled studies in women suffering from vaginal yeast infections qualified for inclusion in our review. In women with uncomplicated vulvovaginal candidosis, single intravaginal doses of clotrimazole 500 mg vaginal tablets provided high cure rates and were as effective as oral azoles. A single dose of clotrimazole 500 mg was equipotent to multiple doses of lower dose strengths. Prolonged treatment regimens proved to be effective in severe and recurrent cases as well as in symptomatic pregnant women. It is therefore expected that in the general population, clotrimazole will continue to be widely used in the field of vaginal health in the upcoming years; more so as clotrimazole resistance in vaginal candidosis is rare. Full article

(This article belongs to the Special Issue Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing)

30 pages, 2056 KiB

Open AccessReview

Current Insights on Antifungal Therapy: Novel Nanotechnology Approaches for Drug Delivery Systems and New Drugs from Natural Sources

by Filipa Sousa, Domingos Ferreira, Salette Reis and Paulo Costa

Pharmaceuticals 2020, 13(9), 248; https://doi.org/10.3390/ph13090248 - 15 Sep 2020

Cited by 81 | Viewed by 10106

Abstract

The high incidence of fungal infections has become a worrisome public health issue, having been aggravated by an increase in host predisposition factors. Despite all the drugs available on the market to treat these diseases, their efficiency is questionable, and their side effects [...] Read more.

The high incidence of fungal infections has become a worrisome public health issue, having been aggravated by an increase in host predisposition factors. Despite all the drugs available on the market to treat these diseases, their efficiency is questionable, and their side effects cannot be neglected. Bearing that in mind, it is of upmost importance to synthetize new and innovative carriers for these medicines not only to fight emerging fungal infections but also to avert the increase in drug-resistant strains. Although it has revealed to be a difficult job, new nano-based drug delivery systems and even new cellular targets and compounds with antifungal potential are now being investigated. This article will provide a summary of the state-of-the-art strategies that have been studied in order to improve antifungal therapy and reduce adverse effects of conventional drugs. The bidirectional relationship between Mycology and Nanotechnology will be also explained. Furthermore, the article will focus on new compounds from the marine environment which have a proven antifungal potential and may act as platforms to discover drug-like characteristics, highlighting the challenges of the translation of these natural compounds into the clinical pipeline. Full article

(This article belongs to the Special Issue Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing)

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