Synthesis of Ester Derivatives of Catechin Isolated from Uncaria gambir and Their Anticancer Activity

Abstract

(+)-Catechin (1) was isolated from the sap of Uncaria gambir and its stereochemistry was confirmed using a polarimeter with an optical rotation value of +17o. Structure modification of compound 1 into several catechin-derived esters was carried out to increase the anticancer activity. Four new catechin-derived esters named catechin-3'-(2,4,6-trichlorobenzoate) (1a), catechin-3'-[2-fluoro-3-(trifluoromethyl)benzoate] (1b), catechin-3'-(4-iodobenzoate) (1c), and catechin-3',4'-[bis(3chlorobenzoate)] (1d) were successfully synthesized via acetylation reaction of compound 1 with various benzoyl chlorides. All five compounds including (+)-catechin (1) were tested for their anticancer activity against HeLa cell lines using the MTT method. The IC50 values of compounds 1, 1a, 1b, 1c, and 1d were 32.59 ± 0.032, 20.23 ± 0.050, 22.83 ± 0,056, 26.02 ± 0.062, and 15.58 ± 0.035 µg/mL, respectively. A combination of molecular docking and molecular dynamics simulation was performed to observe the interaction between catechin derivatives and the SIRT6 enzyme at the molecular level. Molecular studies showed that compounds 1a and 1b have stable interactions with the SIRT6 enzyme through binding affinity studies based on the MM-PBSA and QM/MM-GBSA approaches. Ultimately, modification of the catechin structure into catechin esters increased the anticancer activity of the parent compound.