Synergy of Nitric Oxide and Azoles against Candida Species In Vitro
Open accessAbstract
The candidacidal activity of nitric oxide (NO) as delivered by a class of compounds termed diazeniumdiolates has been investigated. Diazeniumdiolates are stable agents capable of releasing NO in a biologically usable form at a predicted rate, and three such compounds were examined for activity. One compound, ( Z )-1-[ N -(2-aminoethyl)- N -(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO), proved to be most suitable for examining NO activity due to its relatively long half-life (20 h) and because of limited candidacidal activity of the uncomplexed DETA nucleophile. DETA-NO was active against six species of Candida for which the MICs necessary to inhibit 50% growth (MIC 50 s) ranged from 0.25 to 1.0 mg/ml. C. parapsilosis and C. krusei were the most susceptible to the compound. In addition to a determination of NO effects alone, the complex was utilized to investigate the synergistic potential of released NO in combination with ketoconazole, fluconazole, and miconazole. Activity was investigated in vitro against representative strains of Candida albicans , C. krusei , C. parapsilosis , C. tropicalis , C. glabrata , and C. dubliniensis . Determination of MIC 50 , MIC 80 and MICs indicated that DETA-NO inhibits all strains tested, with strains of C. parapsilosis and C. krusei being consistently the most sensitive. The combination of DETA-NO with each azole was synergistic against all strains tested as measured by fractional inhibitory concentration indices that ranged from 0.1222 to 0.4583. The data suggest that DETA-NO or compounds with similar properties may be useful in the development of new therapeutic strategies for treatment of Candida infections.
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The different results between this study and McElhaney-Feser et al. [30] may be due to different experimental design (DETA-NO vs SNP and 37 °C vs 30 °C incubation).
“A previous finding indicated that NO was synergistic with azoles against C. albicans [30], but they did microdilution assays using DETA-NO (Diethylenetriamine NONOate) as the NO donor and 37 °C as the incubation temperature.The different results may be due to the different experimental design.”
From Effect of Nitric Oxide on the Antifungal Activity of Oxidative Stress and Azoles Against Candida albicans (2016) · cites this paper as [30]
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References 36 · Cited by 41
- Authors
- McElhaney-Feser, G. E., Raulli, R. E., & Cihlar, R. L.
- Affiliations
- Georgetown University (US)
- <!--label omitted: 2-->Amulet Pharmaceuticals Inc.,2 Washington, D.C. 20007
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 1998-09
- Volume
- 42
- Issue
- 9
- Pages
- 2342-2346
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC105830
- OpenAlex
- W2164520737
- Cited by
- 41
- References
- 36
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 2 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 6 · 2013: 2 · 2012: 1
- FWCI
- 0.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (P01 AI36251)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Physical Sciences › Chemistry › Organic Chemistry › Antimicrobial agents and applications
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- nitric oxide, diazeniumdiolates, DETA/NO, Candida, antifungal synergy, azoles, ketoconazole, fluconazole, miconazole, Candida parapsilosis, Candida krusei, Candida albicans, Candida tropicalis, Candida glabrata, Candida dubliniensis, candidacidal activity, fractional inhibitory concentration index, minimum inhibitory concentration
- MeSH terms
- Antifungal Agents, Candida, Drug Synergism, Ketoconazole, Miconazole, Microbial Sensitivity Tests, Triazenes, Fluconazole
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