The speciesCandidais a group of opportunistic pathogenic commensals in immune-compromised patients. Treatment ofCandidainfections is becoming increasingly difficult due to antifungal drug resistance, especially with fluconazole (FLC), which is a commonly used azole. In the present study thein vitroantifungal activity of eugenol (EUG) and methyleugenol (MEUG) alone and in combination against 64 FLC-sensitive and 34 FLC-resistant clinicalCandidaisolates is highlighted. All the strains were susceptible to both the naturally occurring phenyl propanoids. The nature of the interaction was studied from fractional inhibitory concentration indices (FICIs) for both EUG plus FLC, and MEUG plus FLC combinations calculated from chequerboard microdilution assays. FICI values depicted a high synergism of FLC with both compounds, which was greatest with MEUG. FLC-resistantCandidaisolates showed high sensitivity to both compounds. No antagonistic activity was seen in the strains tested in the present study. From these results we suggest that EUG and MEUG have great potential as antifungals, and that FLC can be supplemented with EUG and MEUG to treat FLC-resistantCandidainfections.

The increasing incidence of hospital-acquired infections caused by drug-resistant pathogens, host toxicity, the poor efficacy of drugs and high treat

We previously reported the antifungal properties of a monoterpene phenol “Eugenol” against different Candida strains and have observed that the addition of methyl group to eugenol drastically increased its antimicrobial potency. Based on the results and the importance of medicinal synthetic chemistry, we synthesized eugenol-tosylate and its congeners (E1-E6) and tested their antifungal activity against different clinical fluconazole (FLC)- susceptible and FLC- resistant C. albicans isolates alone and in combination with FLC by determining fractional inhibitory concentration indices (FICIs) and isobolograms calculated from microdilution assays. Minimum inhibitory concentration (MIC) results confirmed that all the tested C. albicans strains were variably susceptible to the semi-synthetic derivatives E1-E6, with MIC values ranging from 1–62 μg/ml. The test compounds in combination with FLC exhibited either synergy (36%), additive (41%) or indifferent (23%) interactions, however, no antagonistic interactions were observed. The MICs of FLC decreased 2–9 fold when used in combination with the test compounds. Like their precursor eugenol, all the derivatives showed significant impairment of ergosterol biosynthesis in all C. albicans strains coupled with down regulation of the important ergosterol biosynthesis pathway gene-ERG11. The results were further validated by docking studies, which revealed that the inhibitors snugly fitting the active site of the target enzyme, mimicking fluconazole, may well explain their excellent inhibitory activity. Our results suggest that these compounds have a great potential as antifungals, which can be used as chemosensitizing agents with the known antifungal drugs.

Fungal diseases in humans have increased significantly with the advent of an expanding population of immunosuppressed patients and with the introduction of sophisticated life‐saving medical procedures. Plant extracts and products have been used in traditional medicine for centuries. Coriaria nepalensis essential oil (CNEO) is known to possess antimicrobial activity. This study was an attempt to examine CNEO against various fluconazole‐sensitive and ‐resistant Candida isolates. Insight into the mechanism of action was elucidated by flow cytometric analysis and ergosterol biosynthesis studies. The susceptibility tests for CNEO were carried out in terms of MIC and by disc diffusion assays against all Candida isolates, employing standard protocols. Insight into the mechanism of action was elucidated by propidium iodide cell sorting (FACS) and by assessing ergosterol content in treated and untreated isolates with the test entity. CNEO was found effective against all Candida isolates, including the resistant strains. While CNEO inflicts fungal cell death by disrupting membrane integrity, significant impairment of ergosterol biosynthesis was induced by the test entity. CNEO showed a strong antifungal effect against all the Candida isolates. Mechanisms of action appear to originate from the inhibition of ergosterol biosynthesis and the disruption of membrane integrity. It can be concluded that the observed antimicrobial characteristics of C. nepalensis indicate that it might be a promising antimicrobial agent. Copyright © 2011 John Wiley & Sons, Ltd.