Synthesis and biological evaluation of gallic acid esters as phagocyte oxidative burst inhibitors

Abstract

Several degenerative diseases, including cancer, are caused by oxidative stress, which is caused by the overproduction and accumulation of free radicals. The purpose of the study was to synthesize gallic acid (GA or 3,4,5-trihydroxybenzoic acid) esters and evaluate their anti-inflammatory potential through the inhibition of reactive oxygen species (ROS). The compounds methyl gallate (2), sec-butyl gallate (3), ethyl gallate (4), isopropyl gallate (5), 2-methoxyethyl gallate (6), 4-methoxybutyl gallate (7), 2-methylbutyl gallate (8) and pentan-3-yl gallate (9) were synthesized. 1H NMR, MS and IR data are reported for compounds 2-9, and 13C NMR data for compounds 2, 3, 5, and 6. The molecular formulae of compounds 3 and 7-9 were established by HREI-MS spectroscopic data. All the synthesized compounds were tested for their anti-inflammatory and cytotoxic activities by chemiluminescence and MTT cytotoxicity assay respectively. The results revealed the anti-inflammatory potential of compounds 2-8 with an IC50 range between (13.3 – 54.3 µM) as compared to the standard anti-inflammatory drug, Ibuprofen (IC50 = 54.3 ± 9.2 μM). The most potent inhibitors were found to be compound 3 (ROS IC50 = 15.0 ± 6.6 µM) and compound 7 (ROS IC50 = 13.3 ± 0.8 µM). All compounds were found to be non-cytotoxic in the NIH-3T3 fibroblast cell line. Compounds 3, 7- 9 were identified as new compounds.