Gallic acid from Alchornea glandulosa as a prototype for antifungal semi-synthetic alkyl-gallates

The bioassay-guided approach has been used as a useful tool in the search for active agents of plant origin in our research group. The isolation of several bioactive novel compounds, in addition to unravelling new interesting properties of known plant constituents are some of its attractive features. Gallic acid, a widespread natural compound, was found to possess several pharmacological activities, such as scavenging activity towards DPPH, anticarcinogenic, antimutagenic, antiinflammatory etc. In this study, the previously observed antifungal activity of Alchornea glandulosa Poit. ex Baill. (Euphorbiaceae) ethanol extract and the presence of gallic acid as one of the major constituents, suggested it might be used as model compound for antifungal analogues design [1]. A series of seventeen compounds has been prepared and evaluated for their ability to inhibit human pathogens Candida albicans, C. krusei, C. parapsilosis, and Cryptococcus neoformans by microdilution tests. They presented MICs in the range 3.9 to 250µg/mL and best results were obtained for propyl, butyl, isobutyl and pentyl gallic acid esters against Cryptococcus neoformans. In addition, all the prepared alkyl gallates were tested against phytopathogen fungi Cladosporium sphaerospermum and C. cladosporioides, with best results for ethyl and isopropyl gallates, which displayed detection limit at 10µg. Positive controls fluconazol and nystatin were used for the human pathogens and phytopathogens antifungal assays, respectively. These results suggest the exploration of alkyl gallates might be interesting as leads in the search for new antifungal drugs.

Acknowledgements: Granted by CNPq, CAPES and Biota/BIOprospecTA-FAPESP Program.

References: 1. Romani, A. et al. (2006)J. Pharm. Biomed. Anal. 41, 415–420.