Natural compounds are a suitable alternative to synthetic food preservatives due to their natural origin and health-promoting properties. In the current study, phenolic–phenolic and phenolic–synthetic combinations were tested for their antibiofilm formation, anti-planktonic growth, and anti-adhesion properties against Debaryomyces hansenii, Wickerhamomyces anomalus (formerly Pichia anomala), Schizosaccharomyces pombe, and Saccharomyces cerevisiae. The phenolics were vanillin and cinnamic acid, while the synthetic preservatives were sodium benzoate, potassium sorbate, and sodium diacetate. The vanillin–cinnamic acid combination had synergistic effect in all the tested yeasts for the biofilm inhibition with a fractional inhibitory concentration index (FICI) of ≤0.19 for W. anomalus, 0.25 for S. pombe, 0.31 for S. cerevisiae, and 0.5 for D. hansenii. Most of the phenolic–synthetic combinations had indifferent interaction regarding biofilm formation. The vanillin–cinnamic acid combination also had higher activity against spoilage yeasts adhesion on the abiotic surface and planktonic growth compared to the phenolic–synthetic combinations. For the phenolic–synthetic anti-planktonic activity, synergistic interaction was present in all the vanillin–synthetic combinations in S. pombe, vanillin–sodium benzoate and vanillin–potassium sorbate in S. cerevisiae, vanillin–sodium benzoate in W. anomalus, and cinnamic acid–sodium diacetate in S. pombe. These results suggest a novel antimicrobial strategy that may broaden the antimicrobial spectrum and reduce compound toxicity against food spoilage yeasts.
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