Overview of medically important antifungal azole derivatives

Fromtling, Robert A.

doi:10.1128/cmr.1.2.187

Cited by 346 publications

(195 citation statements)

References 260 publications

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“…The first group of azoles developed was the imidazoles between 1960s and 1980s, such as econazole, miconazole and ketoconazole ( Figure 2F-H) [38]. However, these drugs displayed a variety of limitations, including high toxicity, low efficacy and poor absorbance as well as severe side effects such as liver and gastrointestinal complications [6,39].…”

Section: Current Classes Of Antifungalsmentioning

confidence: 99%

Sphingolipids as Targets for Treatment of Fungal Infections

et al. 2016

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Invasive fungal infections have significantly increased in the last few decades. Three classes of drugs are commonly used to treat these infections: polyenes, azoles and echinocandins. Unfortunately each of these drugs has drawbacks; polyenes are toxic, resistance against azoles is emerging and echinocandins have narrow spectrum of activity. Thus, the development of new antifungals is urgently needed. In this context, fungal sphingolipids have emerged as a potential target for new antifungals, because their biosynthesis in fungi is structurally different than in mammals. Besides, some fungal sphingolipids play an important role in the regulation of virulence in a variety of fungi. This review aims to highlight the diverse strategies that could be used to block the synthesis or/and function of fungal sphingolipids.

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Section: Current Classes Of Antifungalsmentioning

confidence: 99%

Sphingolipids as Targets for Treatment of Fungal Infections

et al. 2016

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“…Croconazole is a synthetic imidazole derivative (phenyl vinyl derivative), which has been shown to be a potent topical antifungal agent against dermatophytes (the causative organisms of tinea infections) and yeasts [Candida albicans] (Thesen, 1995). It has broad spectrum activity against variety of fungal species in vitro (Fromtling, 1988). It has been proved superior to clotrimazole but less active than miconazole and econazole against C. albicans (Ogata et al, 1983).…”

Section: Introductionmentioning

confidence: 99%

“…These tests were carried out using five fungal species, some of them are pathogenic for human and animals, namely Aspergillus flavus, C. albicans, Chrysosporium tropicum (keratinophyte), Penicillium chrysogenum and Trichophyton rubrum (dermatophyte). All fungal strains were selected based on their pharmacological and clinical relevance as reported previously (Ogata et al, 1983;Fromtling, 1988). All fungal species were cultivated on sabouraud-dextrose agar (Oxoid, England).…”

Section: Microbiology Studymentioning

confidence: 99%

Comparative topical delivery of antifungal drug croconazole using liposome and micro-emulsion-based gel formulations

2013

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“…Consequently, there is a need for effective and less toxic drugs for the treatment of patients with these infections. One of these antifungal agents is the triazole fluconazole (Flu) (4,10,14,33,34,41). In vivo experimental studies suggested that Flu is active against disseminated candidiasis (8,9,29,31,32,35,37).…”

mentioning

confidence: 99%

Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans

Etten

Rhee

Kampen

et al. 1991

Antimicrob Agents Chemother

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The effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans were studied. With respect to the extracellular growth of C. albicans, antifungal activity was measured in terms of MICs and minimal fungicidal concentrations as well as by determination of the concentration that effectively killed (>99.9%) C. albicans in the absence or presence (amphotericin B only) of serum. Amphotericin B was highly active in terms of killing, even at an increased inoculum size. In the presence of serum, amphotericin B activity was substantially reduced. For fluconazole, activity was restricted to inhibition of fungal growth, even after the inoculum size was reduced. With respect to the intracellular growth of C. albicans, antifungal activity was measured by using monolayers of murine peritoneal macrophages infected with C. albicans and was measured in terms of inhibition of germ tube formation as well'as effective killing (>99%) of C. albicans. Amphotericin B was highly active against C. albicans. At an increased ratio of infection, amphotericin B activity was slightly reduced. Fluconazole had no antifungal activity. Neither a reduction in the ratio of infection nor exposure of C. albicans to fluconaz'ole prior to macrophage ingestion resulted in activity against intracellular C. albicans by fluconazole. Previous exposure of C. albicans to amphotericin B resulted in increased intracellular activity of amphotericin B. The. intracellular antifungal activity of the combination of fluconazole with amphotericin B was les than that of amphotericin B alone. Amphotericin B showed fungicidal activity against C. albicans growing both extracellularly and intracellularly, whereas fluconazole inhibited growth only of extracellular C. albicans. A slight antagonistic effect between fluconazole and aiflphotericin B was found with respect to intracellular as well as extracellular C. albicans.Deep-seated candidal infections are an important cause of morbidity and mortality in immunocompromised patients (15,21,22). The current drug of choice for most systemic mycoses is still amphotericin B (AmB), but its use is restricted by a variety of toxic side effects (6,13,15,21,22). Consequently, there is a need for effective and less toxic drugs for the treatment of patients with these infections. One of these antifungal agents is the triazole fluconazole (Flu) (4,10,14,33,34,41). In vivo experimental studies suggested that Flu is active against disseminated candidiasis (8,9,29,31,32,35,37). Recently, the antifungal efficacy of Flu was demonstrated in persistently granulocytopenic rabbits when it was used for prevention or early treatment (39,40). Little is still known, however, on the role of Flu in the treatment of systemic candidiasis in immunocompromised patients. Since the host defense mechanisms in these patients are severely impaired, the intrinsic antifungal activity of the antifungal agent is of great importance for effective treatment. Unfortunately, standardized in vitro methods for assessment of ...

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Overview of medically important antifungal azole derivatives

Cited by 346 publications

References 260 publications

Sphingolipids as Targets for Treatment of Fungal Infections

Sphingolipids as Targets for Treatment of Fungal Infections

Comparative topical delivery of antifungal drug croconazole using liposome and micro-emulsion-based gel formulations

Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans

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