Pharmacology, in vitro activity, and in vivo efficacy of new antifungal agents

Wiederhold, Nathan P.

doi:10.1007/s12281-009-0011-0

Cited by 4 publications

(4 citation statements)

References 55 publications

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“…The chemical diversity and known safety profiles of drugs in these libraries (with most having been previously tested in humans) make this a particularly appealing approach with the potential to rapidly advance a candidate into the clinic. To address the shortage of antifungal drugs, particularly those with anti-biofilm activity [ 3 , 24 ], we screened the Repurposing Hub library provided by the Broad Institute [ 16 ] in search for inhibitors of biofilm formation of C. albicans strain SC5314 and C. auris strain 0390. Each of the approximately 6000 compounds in the library, which includes FDA-approved drugs and compounds at different stages of clinical trials [ 16 ], was screened at a final concentration of 20 μM.…”

Section: Resultsmentioning

confidence: 99%

“…But perhaps most interesting is the fact that BAY 11-7082 seems to display potent activity also against all species of filamentous fungi tested, including the Mucorales (both Rhizopus and Mucor species), Aspergillus spp., Scedosporium spp., Lomentospora prolificans , Fusarium spp., Alternaria , Curvularia, and Exserohilum spp., with MICs which, in most instances, compared quite favorably with their corresponding MIC values for voriconazole and/or posaconazole. Of note, infections caused by non-Aspergillus molds are becoming increasingly frequent and are difficult to treat, as many of these species are remarkably recalcitrant to most current existing antifungals, often leading to very poor outcomes in patients suffering from these devastating infections [ 24 ]. As such, developing antifungals with activity against these filamentous fungi represents one of the most pressing needs in the field of medical mycology.…”

Section: Resultsmentioning

confidence: 99%

“…Exserohilum spp., with MICs which, in most instances, compared quite favorably with their corresponding MIC values for voriconazole and/or posaconazole. Of note, infections caused by non-Aspergillus molds are becoming increasingly frequent and are difficult to treat, as many of these species are remarkably recalcitrant to most current existing antifungals, often leading to very poor outcomes in patients suffering from these devastating infections [24]. As such, developing antifungals with activity against these filamentous fungi represents one of the most pressing needs in the field of medical mycology.…”

Section: In Vivo Efficacy Of Ebselen Temsirolimus and Bay 11-7082 In ...mentioning

confidence: 99%

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High-Throughput Screening of the Repurposing Hub Library to Identify Drugs with Novel Inhibitory Activity against Candida albicans and Candida auris Biofilms

Ajetunmobi,

Wall,

Vidal Bonifacio

et al. 2023

JoF

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Candidiasis is one of the most frequent nosocomial infections affecting an increasing number of at-risk patients. Candida albicans remains the most frequent causative agent of candidiasis, but, in the last decade, C. auris has emerged as a formidable multi-drug-resistant pathogen. Both species are fully capable of forming biofilms, which contribute to resistance, increasing the urgency for new effective antifungal therapies. Repurposing existing drugs could significantly accelerate the development of novel therapies against candidiasis. Here, we have screened the Repurposing Hub library from the Broad Institute, containing over 6000 compounds, in search for inhibitors of C. albicans and C. auris biofilm formation. The primary screen identified 57 initial hits against C. albicans and 33 against C. auris. Confirmatory concentration-dependent assays were used to validate the activity of the initial hits and, at the same time, establish their anti-biofilm potency. Based on these results, ebselen, temsirolimus, and compound BAY 11-7082 emerged as the leading repositionable compounds. Subsequent experiments established their spectrum of antifungal activity against yeasts and filamentous fungi. In addition, their in vivo activity was examined in the murine models of hematogenously disseminated C. albicans and C. auris infections. Although promising, further in vitro and in vivo studies are needed to confirm their potential use for the therapy of candidiasis and possibly other fungal infections.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: In Vivo Efficacy Of Ebselen Temsirolimus and Bay 11-7082 In ...mentioning

confidence: 99%

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High-Throughput Screening of the Repurposing Hub Library to Identify Drugs with Novel Inhibitory Activity against Candida albicans and Candida auris Biofilms

Ajetunmobi,

Wall,

Vidal Bonifacio

et al. 2023

JoF

Self Cite

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“…The optimal features of antifungal agents should be fungicidal and should provide options for combination antifungal use, with a favorable pharmacokinetic/ pharmacodynamics profile. Moreover, agents should present a few drug-drug interactions and be administered via both the oral and iv routes [34]. Until recently, there has been no new class of antifungal drugs discovered in over 40 years, and no new class brought into practice since the echinocandins in 2006 [35].…”

Section: Traditional and New Therapeutic Approaches And Mechanism Of ...mentioning

confidence: 99%

Natural Compounds with Antimicrobial Activities in Oral Candida Infections during Head and Neck Radiotherapy

Imperia,

Bonincontro,

Altomare

et al. 2023

Chemotherapy

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Backgrounds: Oral colonization and infections are frequently observed in patients during and soon after radiation therapy (RT). Infective mucositis is a common side effect associated with cancer therapy, characterized by an inflammation of the oral mucous membranes with histological mucosal and submucosal changes. Ulcerative mucositis is responsible for significant pain, impairing the patient's nutritional intake and leading to local or systemic infections promoting mycosis due to several species of the genus Candida. According to international guidelines, treatment of candidiasis depends on the infection site and patient’s condition. Summary: Recently several studies have shown the protective role of natural compounds counteracting the activity of Candida biofilms. The aim of this review is to discuss the antimicrobial activities of natural compounds in fungal infections, especially Candida spp., during and soon after radiotherapy. Indeed new molecules are being discovered and assessed for their capacity to control Candida spp. growth and, probably in the future, will be used to treat oral candidiasis, overall, during radiotherapy. This review reports several preliminary data about preclinical and clinical evidence of their efficacy in the prevention and/or treatment of mucositis due to Radiotherapy with a brief description of the natural compounds with anti-Candida activities. Key messages: The increase in the resistance to the available antifungal drugs related to Candida spp. infections increased as well as drug interactions, urging the development of innovative and more effective agents with antifungal action. Recent preclinical and clinical studies are identifying natural substances with anti-inflammatory and antifungal activity that could be tested in the prevention of candidiasis in patients undergoing radiotherapy. Further studies are needed to confirm these preliminary data.

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Pharmacokinetics, Safety and Efficacy of Voriconazole in Pediatric Patients: An Update

Dokos

Pieper

Lehrnbecher

et al. 2012

Curr Fungal Infect Rep

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Pharmacology, in vitro activity, and in vivo efficacy of new antifungal agents

Cited by 4 publications

References 55 publications

High-Throughput Screening of the Repurposing Hub Library to Identify Drugs with Novel Inhibitory Activity against Candida albicans and Candida auris Biofilms

High-Throughput Screening of the Repurposing Hub Library to Identify Drugs with Novel Inhibitory Activity against Candida albicans and Candida auris Biofilms

Natural Compounds with Antimicrobial Activities in Oral Candida Infections during Head and Neck Radiotherapy

Pharmacokinetics, Safety and Efficacy of Voriconazole in Pediatric Patients: An Update

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