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

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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