Synthesis, In vitro antimicrobial activity, and In silico bioinformatical approach of xanthone-fatty acid esters against Staphylococcus aureus, Escherichia coli, and Candida albicans

Abstract

Microbial infection is gaining attention nowadays due to a high number of active cases and mortality rate. Because of that, research in finding new antimicrobial agents is urgently needed. In this work, we combined the chemical structure of 3-hydroxyxanthone and some fatty acids through ester linkage to form xanthyl laurate, xanthyl myristate, xanthyl palmitate, xanthyl stearate, and xanthyl oleate in 78.68–89.77 % yield. The in vitro antimicrobial assay revealed that xanthyl laurate exhibited the strongest antimicrobial activity with zone of inhibition of 11.0 ± 1.65, 9.43 ± 1.74, and 9.30 ± 1.37 mm against Staphylococcus aureus, Escherichia coli, and Candida albicans, respectively, which also higher than 3-hydoxyxanthone and lauric acid. Xanthyl laurate also yielded minimum inhibition concentration values of 31.25–62.50 μg/mL, which was 2 times lower than of 3-hydroxyxanthone. The structure-based bioinformatical approach indicated that ftsZ S. aureus, MAPK E. coli, and PDE C. albicans are the potential target for xanthyl laurate. Furthermore, both molecular docking and molecular dynamic simulations indicated good stability of xanthyl laurate in the active site of each protein receptor through hydrogen bond and other non-covalent interactions. The in vitro cytotoxicity assay against the NIH3T3 cell line showed that xanthyl laurate was non-toxic at 500 μg/mL with a cell viability percentage of 86.14 ± 1.38 %. This study reports that xanthyl laurate is the most potential antimicrobial agent based on the xanthone-fatty acid ester's structure against S. aureus, E. coli, and C. albicans in both in vitro and in silico assays.