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Updated: Jun 1, 2026

Quantifying the Antifungal Activity of Peptides Against Candida albicans
Published on: January 13, 2023
Terpenoids inhibit Candida albicans growth by affecting membrane integrity and arrest of cell cycle
Gajanan B Zore1, Archana D Thakre, Sitaram Jadhav
1DST-FIST Sponsored School of Life Sciences, SRTM University, Nanded 431606, MS, India. zoreg1@yahoo.co.in
Abstract:
Anti-Candida potential of six terpenoids were evaluated in this study against various isolates of Candida albicans (n=39) and non-C. albicans (n=9) that are differentially susceptible to fluconazole. All the six terpenoids tested, showed excellent activity and were equally effective against isolates of Candida sps., tested in this study. Linalool and citral were the most effective ones, inhibiting all the isolates at ≤0.064% (v/v). Five among the six terpenoids tested were fungicidal. Time dependent kill curve assay showed that MFCs of linalool and eugenol were highly toxic to C. albicans, killing 99.9% inoculum within seven min of exposure, while that of citronellal, linalyl acetate and citral required 15min, 1h and 2h, respectively. FIC index values (Linalool - 0.140, benzyl benzoate - 0.156, eugenol - 0.265, citral - 0.281 and 0.312 for linalyl acetate and citronellal) and isobologram obtained by checker board assay showed that all the six terpenoids tested exhibit excellent synergistic activity with fluconazole against a fluconazole resistant strain of C. albicans. Terpenoids tested arrested C. albicans cells at different phases of the cell cycle i.e. linalool and LA at G1, citral and citronellal at S phase and benzyl benzoate at G2-M phase and induced apoptosis. Linalool, citral, citronellal and benzyl benzoate caused more than 50% inhibition of germ tube induction at 0.008%, while eugenol and LA required 0.032 and 0.016% (v/v) concentrations, respectively. MICs of all the terpenoids for the C. albicans growth were non toxic to HeLa cells. Terpenoids tested exhibited excellent activity against C. albicans yeast and hyphal form growth at the concentrations that are non toxic to HeLa cells. Terpenoids tested in this study may find use in antifungal chemotherapy, not only as antifungal agents but also as synergistic agents along with conventional drugs like fluconazole.
Insights
Six terpenoids show potent anti-Candida activity, with linalool and citral being most effective. These natural compounds are fungicidal and synergistic with fluconazole, offering potential in antifungal chemotherapy.
Area of Science:
- Mycology
- Natural Product Chemistry
- Pharmacology
Background:
- Candida species are significant human pathogens, often developing resistance to azole antifungals like fluconazole.
- Natural products, particularly terpenoids, are being explored for novel antimicrobial properties.
Purpose of the Study:
- To evaluate the anti-Candida activity of six terpenoids against fluconazole-susceptible and -resistant Candida isolates.
- To assess the synergistic potential of these terpenoids in combination with fluconazole.
- To investigate the mechanism of action, including cell cycle arrest and apoptosis induction.
Main Methods:
- Broth microdilution assays to determine Minimum Inhibitory Concentrations (MICs) and Minimum Fungicidal Concentrations (MFCs).
- Checkerboard assays to evaluate Fractional Inhibitory Concentration (FIC) index for synergy with fluconazole.
- Time-dependent kill curve assays and cell cycle analysis.
- Germ tube induction inhibition assays and cytotoxicity assessment against HeLa cells.
Main Results:
- All six terpenoids demonstrated significant anti-Candida activity, with linalool and citral being the most potent.
- Five terpenoids exhibited fungicidal activity.
- Synergistic effects were observed when terpenoids were combined with fluconazole against resistant strains.
- Terpenoids induced cell cycle arrest and apoptosis in Candida albicans without toxicity to human HeLa cells.
Conclusions:
- The evaluated terpenoids possess strong antifungal properties and can overcome fluconazole resistance.
- Their non-toxic nature and synergistic potential make them promising candidates for development as antifungal agents or adjuncts in combination therapy.
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