Heterogeneity of action of mechanisms among antimycotic imidazoles

Sud, Inder Jit; Feingold, David S.

doi:10.1128/aac.20.1.71

Cited by 124 publications

(67 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several lipophilic antimicrobial agents can exert their activity either through direct damage of the cell membrane or by interfering with metabolic pathways. This is the case, for example, with the lipophilic azoles [30,31], butena®ne [32] and phenothiazines [33,34]. In those studies, the concentrations needed to produce direct membrane damage were higher than those producing metabolic imbalance.…”

Section: Discussionmentioning

confidence: 94%

Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species

Pina-Vaz

Sansonetty

Rodrigues

et al. 2000

Journal of Medical Microbiology

106

View full text Add to dashboard Cite

Ibuprofen, a non-steroidal anti-in¯ammatory drug, exhibited antimicrobial activity against Candida albicans and non-albicans strains. At 10 mg=ml, ibuprofen showed a rapid cidal activity against exponential growth phase C. albicans, accompanied by rapid and extensive leakage of intracellular K , permeation to propidium iodide, lysis of spheroplasts and severe membrane ultrastructural alterations. These results indicate that the killing of Candida cells is due to direct damage to the cytoplasmic membrane. At 5 mg=ml, ibuprofen inhibited growth; however, it did not kill the yeasts and did not directly affect the cytoplasmic membrane. Evaluation of yeast metabolic vitality with thē uorescent probe FUN-1 showed that growth inhibition induced by the fungistatic drug concentration was due to metabolic alterations. The combination of ibuprofen with uconazole resulted in synergic activity with eight of the 12 Candida strains studied, including four of the ®ve¯uconazole-resistant strains. The MICs of¯uconazole for thē uconazole-resistant strains decreased 2±128-fold when the drug was associated with ibuprofen. When in combination with¯uconazole, MICs for ibuprofen decreased by up to 64-fold for all the 12 strains studied. These results point to the practicability of using ibuprofen, alone or in combination with azoles, in the treatment of candidosis, particularly when applied topically, taking advantage of the drug's antifungal and antiin¯ammatory properties.

show abstract

Section: Discussionmentioning

confidence: 94%

Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species

Pina-Vaz

Sansonetty

Rodrigues

et al. 2000

Journal of Medical Microbiology

106

View full text Add to dashboard Cite

show abstract

“…Varied test conditions by different groups of investigators have produced confusing data concerning the fungistatic versus fungicidal activity in this class of antifungal drugs (173,289,290). Sud and Feingold (289,290) demonstrated that both miconazole and clotrimazole exerted direct physicochemical cell membrane damage on yeast cells that was a lethal event; interestingly, ketoconazole did not demonstrate lethal activity in this assay.…”

Section: Proposed Modes Of Action Of Antifungal Azole Derivativesmentioning

confidence: 99%

Overview of medically important antifungal azole derivatives

1988

View full text Add to dashboard Cite

Fungal infections are a major burden to the health and welfare of modern humans. They range from simply cosmetic, non-life-threatening skin infections to severe, systemic infections that may lead to significant debilitation or death. The selection of chemotherapeutic agents useful for the treatment of fungal infections is small. In this overview, a major chemical group with antifungal activity, the azole derivatives, is examined. Included are historical and state of the art information on the in vitro activity, experimental in vivo activity, mode of action, pharmacokinetics, clinical studies, and uses and adverse reactions of imidazoles currently marketed (clotrimazole, miconazole, econazole, ketoconazole, bifonazole, butoconazole, croconazole, fenticonazole, isoconazole, oxiconazole, sulconazole, and tioconazole) and under development (aliconazole and omoconazole), as well as triazoles currently marketed (terconazole) and under development (fluconazole, itraconazole, vibunazole, alteconazole, and ICI 195,739).

show abstract

“…5 and 6A support an antibiotic mechanism for miconazole involving NOD inhibition. Nevertheless, at these relatively high miconazole concentrations, the increased NO sensitivity of S. cerevisiae could also be due in part to miconazole impairment of membrane synthesis, membrane integrity, and other cell functions (1,30,53,58). Under conditions mimicking microaerobic C. albicans infection, 160 ppm NO gas exposure (Ͻ0.3 M in solution) also showed strong inhibition of the growth of the NOD-deficient C. albicans mutant (⌬YHB1) but not the isogenic parental strain RM1000 (Fig.…”

Section: Imidazoles Inhibit No Metabolism In Microbesmentioning

confidence: 99%

Imidazole Antibiotics Inhibit the Nitric Oxide Dioxygenase Function of Microbial Flavohemoglobin

Helmick

Fletcher

Gardner

et al. 2005

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Flavohemoglobins metabolize nitric oxide (NO) to nitrate and protect bacteria and fungi from NO-mediated damage, growth inhibition, and killing by NO-releasing immune cells. Antimicrobial imidazoles were tested for their ability to coordinate flavohemoglobin and inhibit its NO dioxygenase (NOD) function. Miconazole, econazole, clotrimazole, and ketoconazole inhibited the NOD activity of Escherichia coli flavohemoglobin with apparent K i values of 80, 550, 1,300, and 5,000 nM, respectively. Saccharomyces cerevisiae, Candida albicans, and Alcaligenes eutrophus enzymes exhibited similar sensitivities to imidazoles. Imidazoles coordinated the heme iron atom, impaired ferric heme reduction, produced uncompetitive inhibition with respect to O 2 and NO, and inhibited NO metabolism by yeasts and bacteria. Nevertheless, these imidazoles were not sufficiently selective to fully mimic the NO-dependent growth stasis seen with NOD-deficient mutants. The results demonstrate a mechanism for NOD inhibition by imidazoles and suggest a target for imidazole engineering.

show abstract

Heterogeneity of action of mechanisms among antimycotic imidazoles

Cited by 124 publications

References 17 publications

Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species

Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species

Overview of medically important antifungal azole derivatives

Imidazole Antibiotics Inhibit the Nitric Oxide Dioxygenase Function of Microbial Flavohemoglobin

Contact Info

Product

Resources

About