FLA94, an isatin derivative, inhibits Candida albicans growth by inducing membrane damage and ROS overaccumulation

Infections caused by Candida albicans pose a significant clinical challenge worldwide due to their opportunistic nature and resistance to treatment.

Here, compounds derived from isatin were evaluated for pharmacological and antifungal potential against C. albicans.

Out of 19 compounds, only the compound FLA94 reduced the cell viability of C. albicans by 90% at 50 μM. The minimal inhibitory concentration (MIC) to reach 50% of inhibition (MIC50) was calculated at 42.8 μM. Fluorescence analysis revealed that FLA94 increased fungal cell membrane permeabilization and the overproduction of reactive oxygen species (ROS). Bioinformatic analyses predicted that FLA94 has good gastrointestinal absorption and low toxicity, calculating the LD50 around 3000 mg kg^-1 without significant risk of adverse effects. Target fishing and molecular docking analyses predicted that FLA94 targeted an11d interacted with Secreted Aspartic Peptidase type 2 (SAP2) and an Agglutinin-Like Protein 3 (ALS3) key enzymes for C. albicans virulence and biofilm establishment.

These promising results suggest that satin-derivatives can potentially treat infectious diseases caused by C. albicans.