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Deuterated Curcuminoids: Synthesis, Structures, Computational/Docking and Comparative Cell Viability Assays against Colorectal Cancer
Author(s) -
Laali Kenneth K.,
Zwarycz Angela T.,
Bunge Scott D.,
Borosky Gabriela L.,
Nukaya Manabu,
Kennedy Gregory D.
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900179
Subject(s) - chemistry , cytotoxicity , adduct , viability assay , docking (animal) , stereochemistry , deuterium , colorectal cancer , in vitro , cell culture , mtt assay , biochemistry , cancer , biology , organic chemistry , medicine , physics , nursing , quantum mechanics , genetics
A series of deuterated curcuminoids (CUR) were synthesized, bearing two to six OCD 3 groups, in some cases in combination with methoxy groups, and in others together with fluorine or chlorine atoms. A model ring‐deuterated hexamethoxy‐CUR–BF 2 and its corresponding CUR compound were also synthesized from a 2,4,6‐trimethoxybenzaldehyde‐3,5‐d 2 precursor. As with their protio analogues, the deuterated compounds were found to remain exclusively in the enolic form. The antiproliferative activities of these compounds were studied by in vitro bioassays 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–BF 2 adducts exhibited better overall growth inhibition by NCI‐60 assay, while for other CUR–BF 2 adducts the non‐deuterated analogues were more cytotoxic. Results of the more focused comparative cell viability assays followed the same trend, but with some variation depending on cell lines. The CUR–BF 2 adducts exhibited significantly higher cytotoxicity than CURs. Structural studies (X‐ray and DFT) and computational molecular docking calculations comparing their inhibitory efficacy with those of known anticancer agents used in chemotherapy are also reported.