Synthesis, crystal structure, and growth inhibition of human hepatoma cell (HepG2) of polyphenolic compounds based on gallates

Seven compounds (1-7) based on gallate were synthesized and characterized by elemental analysis, H-1 NMR, and MS spectra. 2-(3,5-Dibenzyloxy-4-methoxy)phenyl-2-propanol (6) was a new compound. Methyl 3,5-dihydroxy-4-methoxybenzoate (3), methyl 3,5-dibenzyloxy-4-methoxybenzoate (4), 3,5-dibenzyloxy-4-methoxybenzyl alcohol (5), and compound 6 were structurally determined by single-crystal X-ray diffraction for the first time. Crystallographic data for 3: space group P2(1)2(1)2(1); a = 4.0750(8) angstrom, b 7.5880(15) angstrom, c = 29.802(6) angstrom; V = 921.5(3) angstrom; Z = 4. 4: space group P-1; a = 10.068(2) angstrom, b = 10.499(2) angstrom, c = 11.388(2) angstrom; alpha = 76.84(3)degrees, beta = 66.79(3)degrees, gamma = 64.10(3)degrees; V = 993.0(3) angstrom(3), Z = 2. 5: space group P-1; a = 8.1410(16) angstrom, b = 8.7590(18) angstrom, c = 12.879(3) angstrom; alpha 91.66(3)degrees, beta = 94.69(3)degrees, gamma = 91.73(3)degrees; V = 914.4(3) angstrom(3); Z = 2. 6: space group P2(1)lc; a = 5.8100(12) angstrom, b = 15.778(3) angstrom, c = 23.237(5) angstrom; beta = 96.09(3)degrees; V = 2118.1(7) angstrom(3); Z = 4. All of the seven compounds were evaluated for the inhibition of growth of human hepatoma (HepG2) cells. Comparison with the positive-control 5-fluorouracil (IC50 51.6 mu mol/L), 5 showed stronger cytotoxic activity with an IC50 around 15.3 mu mol/L, while IC50 value of 3 was 90.3 mu mol/L. The effect of slight structural variations in this series of compounds was found to cause a marked change in their activity against HepG2 cells.