Inhibition of ergosterol synthesis in Candida albicans by novel eugenol tosylate congeners targeting sterol 14α-demethylase (CYP51) enzyme

  • Shabir Ahmad Lone
  • Shama Khan
  • Aijaz AhmadEmail author
Original Paper


This study is a continuation and extension of our previous study in which we synthesized seven novel eugenol tosylate congeners (ETC-1 to ETC-7) from a natural compound eugenol and checked their antifungal activity against different isolates of Candida albicans. All these ETCs showed potent antifungal activity to varying degrees. In this study, the aim is to evaluate the effect of most active compounds (ETC-5, ETC-6 and ETC-7) on ergosterol biosynthesis pathway and cellular viability in C. albicans by applying combined approach of in silico and in vitro methodologies. In silico studies were done through all atom molecular mechanics approach and free binding energy estimations, and in vitro study was done by estimating total intracellular sterol content and effect on expression of ERG11 gene. Furthermore, effect on cell viability by these compounds was also tested. Our results demonstrated that these ETCs target ergosterol biosynthesis pathway in C. albicans by inhibiting the lanosterol 14-α demethylase enzyme and also downregulates expression of its related gene ERG11. Furthermore, these ETCs exhibit potent fungicidal effect in cell viability assay, thus overall results advocating the claim that these tosylates have potential to be taken to next level of antifungal drug development.


Eugenol tosylates congeners C. albicans Ergosterol Molecular docking 


Author contributions

Conceived and designed the experiments: AASK. Performed the experiments: SAL. Analyzed the data: SAL, SK, AA. Contributed reagents/materials/analysis tools: AA. Wrote the paper: SAL.


We gratefully acknowledge financial support from University Research Committee Grant for 2019—Friedel Sellschop Award (Grant no: AZMD019), Wits Faculty of Health Sciences Research Committee (FRC, Grant no: 001…5254) and South Africa Medical Research Council (MRC) (Grant no: MLEP016).

Compliance with ethical standards

Conflict of interest

We have no competing interests to declare.

Ethical approval

This study was approved by the Human Research Ethics Committee of University of the Witwatersrand (Johannesburg, South Africa). Existing stock cultures of C. albicans used in this study were stored in the Department of Clinical Microbiology and Infectious Diseases, University of the Witwatersrand, Johannesburg, South Africa.

Supplementary material

203_2019_1781_MOESM1_ESM.docx (134 kb)
Supplementary file1 (DOCX 134 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Clinical Microbiology and Infectious Diseases, School of Pathology, Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa
  2. 2.Infection Control, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory ServiceJohannesburgSouth Africa

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