Three new derivatives of tetrahydrocurcumin 6, 7 and 9 have been prepared as potent antitumor agents using copper(II)-catalyzed 'click chemistry'. Their structures were identified using 1H-NMR, 13C-NMR and HRMS techniques. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay has been carried out to investigate the in vitro cytotoxicity against human cervical carcinoma (HeLa), human lung adenocarcinoma (A549), human hepatoma carcinoma (HepG2) and human colon carcinoma (HCT-116). Compound 6 has showed significant inhibitory activity against HCT-116 cell line with an IC50 value of 17.86 μM compared to tetrahydrocurcumin (50.96 μM) and positive control etoposide (19.48 μM) while showed no inhibitory activity against NCM460 cell line. Compounds 7 showed moderate inhibitory activity compared to tetrahydrocurcumin and etoposide while compound 9 showed no obvious inhibitory activity. The results suggested further structure modifications of tetrahydrocurcumin to improve its anticancer activity.[Formula: see text].
Keywords: Tetrahydrocurcumin; antitumor activity; click reaction; drug discovery; podophyllotoxin.