Deuterated Curcuminoids: Synthesis, Structures, Computational/Docking and Comparative Cell Viability Assay against Colorectal Cancer.

Deuterated Curcuminoids: Synthesis, Structures, Computational/Docking and Comparative Cell Viability Assay against Colorectal Cancer. ChemMedChem. 2019 Apr 17;: Authors: Laali KK, Zwarycz A, Bunge S, Borosky G, Nukaya M, Kennedy G Abstract A series of deuterated curcuminoids were synthesized, bearing two to six OCD3 groups, in some cases in combination with OCH3 groups, and in others together with fluorines. A model ring deuterated hexamethoxy-CUR-BF2 and its corresponding CUR compound were also synthesized form a 2,4,6-trimethoxybenzaldehyde-3,5-d2 precursor. As with their protio-analogues, the deuterated compounds remained exclusively in the keto-enolic form. The anti-proliferative activity of these compounds were studied by in-vitro bioassay against a panel of 60 cancer cell lines, and more specifically in human colorectal cancer (CRC) cells (HCT116, HT29, DLD-1, RKO, SW837, and Caco2) and in normal colon cells (CCD841CoN). The deuterated CUR-BF2 adducts 3 and 11 exhibited better overall growth inhibition by NCI-60 assay, while for other CUR-BF2 adducts the non-deuterated analogues (1a, 5a, 7a, and 9a) were more cytotoxic. More focused comparative cell viability assay followed the same trend but with some variation depending on cell lines. The CUR-BF2 adducts exhibited significantly higher cytotoxicity compared to CURs. Structural studies (X-ray and DFT), and computational molecular docking calculations comparing their inhibitory ...
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research