scholarly journals Current and Emerging Azole Antifungal Agents

1999 ◽  
Vol 12 (1) ◽  
pp. 40-79 ◽  
Author(s):  
Daniel J. Sheehan ◽  
Christopher A. Hitchcock ◽  
Carol M. Sibley
Keyword(s):  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Fungal Infections ◽  
Mechanisms Of Action ◽  
Current Status ◽  
In Vitro Susceptibility ◽  
Clinical Resistance ◽  
In Vitro Susceptibility Testing

SUMMARY Major developments in research into the azole class of antifungal agents during the 1990s have provided expanded options for the treatment of many opportunistic and endemic fungal infections. Fluconazole and itraconazole have proved to be safer than both amphotericin B and ketoconazole. Despite these advances, serious fungal infections remain difficult to treat, and resistance to the available drugs is emerging. This review describes present and future uses of the currently available azole antifungal agents in the treatment of systemic and superficial fungal infections and provides a brief overview of the current status of in vitro susceptibility testing and the growing problem of clinical resistance to the azoles. Use of the currently available azoles in combination with other antifungal agents with different mechanisms of action is likely to provide enhanced efficacy. Detailed information on some of the second-generation triazoles being developed to provide extended coverage of opportunistic, endemic, and emerging fungal pathogens, as well as those in which resistance to older agents is becoming problematic, is provided.

scholarly journals New sulfone and sulfanyl derivatives with antifungal activity

2018 ◽  
pp. 175-184
Author(s):  
Małgorzata Gizińska ◽  
Marzena Połaska ◽  
Zbigniew Ochal ◽  
Monika Staniszewska
Keyword(s):  
Antifungal Agents ◽  
Fungal Infections ◽  
In Vitro Susceptibility ◽  
Microdilution Method ◽  
Alternative Approach ◽  
Broth Microdilution Method ◽  
Fungal Morphogenesis ◽  
In Vitro Susceptibility Testing ◽  
Base Structure

Introduction: Increasing occurrence of fungal infections raises the need to develop novel antifungal agents. In this context, an inhibition of morphological switch may provide an alternative approach to find compounds with a potential to control the Candida albicans infections. Methods: A series of 17 sulfone and sulfanyl derivatives was synthesized and evaluated for activity against the C. albicans wild type (SC5314, ATCC) and SAP-deficient mutant strains using the broth microdilution method M27-A3. Afterwards, phase-contrast microscopy was applied to evaluate the inhibition of fungal morphogenesis under the influence of randomly selected active compounds: 1, 5 and 6. Results: By in vitro susceptibility testing of C. albicans, we identified the effective antifungal agents displaying moderate-to-good activity. Newly synthesized sulfanyl and sulfone derivatives strongly inhibited the C. albicans morphogenetic transition under the hyphae inducing conditions. Conclusions: The leading compound 6 has the potential to be used as a base structure in antifungal drug development, however further structural optimalization and toxicity studies are required.

In vitro Susceptibility Testing of Candida Isolates from Clinical Specimens to Four Antifungal Agents

Chemotherapy ◽  
1990 ◽  
Vol 36 (6) ◽  
pp. 396-402 ◽  
Author(s):  
Mitsuo Ohkawa ◽  
Shuji Tokunaga ◽  
Mitsuhiro Takashima ◽  
Tadayuki Nishikawa ◽  
Haruo Hisazumi ◽  
...  
Keyword(s):  
Antifungal Agents ◽  
Susceptibility Testing ◽  
In Vitro Susceptibility ◽  
Clinical Specimens ◽  
In Vitro Susceptibility Testing

scholarly journals Antifungal Activity of Tamoxifen: In Vitro and In Vivo Activities and Mechanistic Characterization

2009 ◽  
Vol 53 (8) ◽  
pp. 3337-3346 ◽  
Author(s):  
Kristy Dolan ◽  
Sara Montgomery ◽  
Bradley Buchheit ◽  
Louis DiDone ◽  
Melanie Wellington ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Tube Formation ◽  
In Vivo Model ◽  
In Vitro Susceptibility ◽  
In Vitro Susceptibility Testing ◽  
Treat Breast Cancer

ABSTRACT Tamoxifen (TAM), an estrogen receptor antagonist used primarily to treat breast cancer, has well-recognized antifungal properties, but the activity of TAM has not been fully characterized using standardized (i.e., CLSI) in vitro susceptibility testing, nor has it been demonstrated in an in vivo model of fungal infection. In addition, its mechanism of action remains to be clearly defined at the molecular level. Here, we report that TAM displays in vitro activity (MIC, 8 to 64 μg/ml) against pathogenic yeasts (Candida albicans, other Candida spp., and Cryptococcus neoformans). In vivo, 200 mg/kg of body weight per day TAM reduced kidney fungal burden (−1.5 log10 CFU per g tissue; P = 0.008) in a murine model of disseminated candidiasis. TAM is a known inhibitor of mammalian calmodulin, and TAM-treated yeast show phenotypes consistent with decreased calmodulin function, including lysis, decreased new bud formation, disrupted actin polarization, and decreased germ tube formation. The overexpression of calmodulin suppresses TAM toxicity, hypofunctional calmodulin mutants are hypersensitive to TAM, and TAM interferes with the interaction between Myo2p and calmodulin, suggesting that TAM targets calmodulin as part of its mechanism of action. Taken together, these experiments indicate that the further study of compounds related to TAM as antifungal agents is warranted.

scholarly journals Comparative Study of Susceptibilities of Germinated and Ungerminated Conidia of Aspergillus fumigatus to Various Antifungal Agents

1999 ◽  
Vol 37 (3) ◽  
pp. 858-861 ◽  
Author(s):  
Elias K. Manavathu ◽  
Jessica Cutright ◽  
Pranatharthi H. Chandrasekar
Keyword(s):  
Comparative Study ◽  
Growth Inhibition ◽  
Aspergillus Fumigatus ◽  
Mycelial Growth ◽  
Fungicidal Activity ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
In Vitro Susceptibility ◽  
In Vitro Susceptibility Testing

Conidia are used as inocula for the in vitro susceptibility testing of Aspergillus fumigatus. Since the MIC is defined on the basis of visible mycelial growth, conidia should germinate and produce sporelings (germinated conidia) for monitoring of the growth inhibition and fungicidal activity of a drug. If a compound is capable of inhibiting germination of conidia while affecting or not affecting the growth of the organism, the MIC obtained will be the concentration of the drug required for the inhibition of conidial germination but not necessarily that required for inhibition of the growth of the organism. We investigated the susceptibility of germinated and ungerminated conidia to amphotericin B, itraconazole, voriconazole, and SCH56592. The MICs of various antifungal agents for germinated conidia were almost identical to those obtained for ungerminated conidia. In addition, both the germinated and ungerminated conidia were killed with almost equal efficiency by all of the compounds tested when exposed to the drugs for 24 h. These results suggest that either germinated or ungerminated conidia could be used as inocula for in vitro susceptibility studies of A. fumigatus with identical results.

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