Integrative in vitro and in silico assessment of bicyclic monoterpenes as antifungal agents targeting the cell membrane integrity of Candida albicans.

Authors

Parveen, Nafis Raj, Abdus Samad, Shabana Khatoon, Umaira Mirza, Shama Parveen, Nikhat Manzoor

Published in

Archives of microbiology. Volume 208. Issue 6. Apr 07, 2026. Epub Apr 07, 2026.

Abstract

The yeast Candida is a common component of the human microbiota. An imbalance in the colonization of this commensal form can lead to an infection that presents symptoms ranging from mild localized rashes to severe disseminated disease. The primary treatment for candidiasis typically includes antifungal drugs belonging to the class of azoles that target cell membranes. Given the substantial rise in resistance to antifungal medications in recent years, it is imperative to explore novel therapeutic options for managing candidiasis, which has emerged as a significant medical challenge. Plant-derived compounds possessing antifungal properties, particularly monoterpenes, have been recognized as promising alternatives. However, while acyclic and monocyclic monoterpenes have been extensively investigated, bicyclic monoterpenes have not received adequate attention. Our aim was to assess the antifungal potential of nopol and myrtenol, two bicyclic monoterpenes, against Candida albicans. Broth microdilution assays demonstrated the inhibition of fungal growth, with minimum inhibitory concentration (MIC) values of 878 and 1681 µM, respectively. The compounds were examined for their impact on membrane integrity by estimation of ergosterol content, scanning electron microscopy, fluorescence microscopy, propidium iodide (PI) uptake, and H⁺-extrusion studies. They have been studied for their effect on the cell wall by the sorbitol protection assay and cell wall components by Calcofluor white and Congo red. In silico studies also showed that the mechanism of antifungal action involved the disruption of the cell membrane. Hemolytic activity assays indicated minimal erythrocyte lysis at MIC concentrations, suggesting low cytotoxicity toward red blood cells. The results indicate that the selected monoterpenes represent safer natural antifungal agents, which may work by disrupting membrane integrity, inhibiting ergosterol biosynthesis and other membrane-associated structures.

PMID:
41944880
Bibliographic data and abstract were imported from PubMed on 07 Apr 2026.

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