Abstract
Ocular fungal infections are slow-progressing conditions that primarily affect the cornea but can also involve the entire eyeball. Candida albicans is one of the most involved species. Both diagnosing and treating these infections require prompt and effective action. However, the currently available treatment options mainly rely on azoles and polyenes, which are known for their poor penetration into ocular tissue and associated toxicity. Moreover, conventional antifungals are usually ineffective when tested against biofilm-associated infections, mainly due to the metabolically inactive state of dormant cells embedded in the extracellular biofilm matrix. Here, analysis of the in vitro antifungal activity of four 2-aminobenzoic acid derivatives synthesized using a green method and their combination with Fluconazole (FLC) showed efficacy against the FLC-resistant clinical isolate of C. albicans under both planktonic and biofilm formation conditions. Results showed that compounds 1 and 2 exhibited the best antifungal activity in the checkerboard association test, presenting a synergistic effect towards antifungal action. The downregulation of HWP, ERG11, and ASL3 genes during biofilm inhibition suggested a reduced capacity of the four compounds for hyphal growth and adhesion, as well as a decrease in pathogenicity due to the downregulation of some SAP genes. In vitro and in vivo toxicity profiles indicated that these compounds exhibited low toxicity, as well as the absence of genotoxic effects. Therefore, green-synthetized 2-aminobenzoic acid derivatives may have potential as antifungal agents for the inhibition of C. albicans growth and biofilm formation.