Assessment of antifungal and anti-biofilm potential of essential oil active constituents alone and in combinatorial mode of limonene and linalool against Candida albicans and Candida tropicalis.

Opportunistic Candidiasis is rising among immunocompromised and elderly patients, with increasing antifungal resistance. This study evaluated five essential oil-derived compounds against Candida albicans and Candida tropicalis. Limonene showed the strongest antifungal activity, with minimum inhibitory concentration (MICs) of 32-64 µg/mL. Similarly, biofilm inhibition/eradication concentration (BIC/BEC) was found in followed the order: limonene > linalool > 1,8-cineole = 2-undecanone = borneol. Notably, the combination of limonene and linalool showed additive effects, with fractional inhibitory concentration index (FICI) values of 0.79 for C. albicans and 0.98 for C. tropicalis. This combinatorial approach, investigated for the first time, showed no significant cytotoxicity on human embryonic kidney (HEK-293) and human keratinocyte (HaCaT) cell lines. A co-culture model of Candida spp. and HaCaT cells was developed to study host-pathogen interactions and antifungal efficacy. Results highlight EO-ACs, especially limonene and linalool, as promising alternatives against resistant Candida infections.