Structure-Activity Relationship of Novel Antifungal Small Molecule against Candida

Method: First, in a screening assay we examined the minimum inhibitory concentration (MIC) of SM21 and its analogues  against C. albicans reference strains. Amphotericin B was used as the positive control. Next, we used Candida clinical isolates derived from denture stomatitis and nasopharyngeal carcinoma (NPC) patients to evaluate the efficacy of small molecules using disc diffusion assay.  Mechanism of action of small molecule analogues against Candida was examined by membrane permiabilization assay of propodium Iodide (PI) intake using Confocal Laser Scanning Microscopy. Bacterial species Streptococcus mutans, Escherichia coli were used to evaluate the specificity of SM21 and its analogues. 

Results: MICs of the SM21 and amphotericin B against C. albicans reference strains were 0.2 µg/ml. Out of the analogues examined only a single analogue SM63 showed comparable activity having  MIC of  0.2 µg/ml.  Both SM21 and SM63 were effective against Candida isolates derived from denture stomatitis and NPC patients. Membrane permiabilization assay showed that SM21 and SM63 may act on Candida cell wall. Activity of SM21 and SM63 was fungal specific as there was no effect on bacterial species.

Conclusion: Present study demonstrated that novel antifungal small molecules SM21 and SM63 could be developed as a new-class of antifungal agent against Candida infections, which could bring enormous clinical benefits (HKU Seed funding for CJS & LPS).