<p><i>Candida albicans</i> biofilms are difficult to eradicate because early adhesion and hyphal development promote surface colonization and antifungal tolerance. This study evaluated commercially obtained synthetic cinnamyl acetate (CA; ≥98%) as a defined antivirulence candidate against <i>C. albicans</i> ATCC 10231. CA showed reproducible antifungal and antibiofilm activity, with MIC = 125 ± 5&#xa0;µg/mL and MBIC = 180 ± 7&#xa0;µg/mL, and was the most active ester in the comparator screen. At 0.5× MBIC, CA reduced early adhesion by 39%, decreased the hyphal fraction from 0.74 to 0.21, and down-regulated the hypha-associated markers <i>HWP1</i> and <i>ALS3</i> while planktonic viability and SYTOX Green uptake remained near baseline. Exploratory docking was compatible with an adhesin-associated working hypothesis, but direct target engagement was not demonstrated. Overall, synthetic CA is best interpreted as a proof-of-concept anti-adhesion lead rather than a confirmed adhesin inhibitor or stand-alone fungicidal agent. These findings provide a defined experimental framework for future validation in additional <i>Candida</i> strains, epithelial co-culture models, and biochemical target-engagement assays.</p>

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Synthetic Cinnamyl Acetate as a Candidate Inhibitor of Candida albicans Biofilms with an Adhesin-Associated Anti-Adhesion Phenotype: Evidence from Molecular Docking and Antifungal Assays

  • Dang Anh Tuan,
  • Jan Masak

摘要

Candida albicans biofilms are difficult to eradicate because early adhesion and hyphal development promote surface colonization and antifungal tolerance. This study evaluated commercially obtained synthetic cinnamyl acetate (CA; ≥98%) as a defined antivirulence candidate against C. albicans ATCC 10231. CA showed reproducible antifungal and antibiofilm activity, with MIC = 125 ± 5 µg/mL and MBIC = 180 ± 7 µg/mL, and was the most active ester in the comparator screen. At 0.5× MBIC, CA reduced early adhesion by 39%, decreased the hyphal fraction from 0.74 to 0.21, and down-regulated the hypha-associated markers HWP1 and ALS3 while planktonic viability and SYTOX Green uptake remained near baseline. Exploratory docking was compatible with an adhesin-associated working hypothesis, but direct target engagement was not demonstrated. Overall, synthetic CA is best interpreted as a proof-of-concept anti-adhesion lead rather than a confirmed adhesin inhibitor or stand-alone fungicidal agent. These findings provide a defined experimental framework for future validation in additional Candida strains, epithelial co-culture models, and biochemical target-engagement assays.