In Silico Study, Synthesis, and Cytotoxic Activity of Esterification of Eugenol and Gallic Acid Against HT-29 Cell Line

Abstract

Eugenol and gallic acid have cytotoxic effects in HT-29 colon cancer cells. In this study, we examined cytotoxic effect of esterification of eugenol and gallic acid. Before synthesized process, in silico docking was conduct to eugenol, gallic acid and its esterification products against Bcl-2 protein. After in silico docking, Eugenol and gallic acid were allowed to react by Mitsunobu Reaction to obtain compound (4-5). Proton and carbon NMR spectroscopy, also mass spectra (GCMS) were used to characterize of the structure from products. The products from esterification were tested by cytotoxic activity and showed by IC 50 with navitoclax as positive control. In silico docking result showed compound (5) had the lowest Gibb's Energy. Compound 4 and 5 were successfully synthesized and characterized by spectrometer 1 H-NMR, 13 C-NMR, and mass spectrometry. In silico docking result related to cytotoxic assay against HT-29 cell line. By replacing hydroxyl group of gallic acid with methoxy groups had increased the lipophilicity and the cytotoxicity. The greatest inhibitor against HT-29 cell line was compounds (5) with IC 50 values of 22.81 µg/ml. The synthesized esterification product, compound (5), had greater cytotoxic activity than eugenol and gallic acid against colon cancer cell line, HT-29. Thus, the esterification products should be considered as a promising candidate for cancer colon drug.

Investigating the Impact of Eugenol on the Suppression of Gallic Acid Oxidation by Employing Cyclic Voltammetry

“…On the other hand, Eug is the natural constituent of clove, basil, cinnamon and other variety of plants [23]. It is to be noted that Eug being a phenol, (i.e., allyl chain-substituted guaiacol) and GA a phenolic acid are generally expected to undergo esteri cation reaction [24]. However, it has been extensively shown in numerous previous works that phenolic acids can considerably react with phenols to form esters only in the presence of particular catalysts [25].…”