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

Academic Article

Abstract

  • A series of deuterated curcuminoids (CUR) were synthesized, bearing two to six OCD 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 and its corresponding CUR compound were also synthesized from a 2,4,6-trimethoxybenzaldehyde-3,5-d 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 adducts exhibited better overall growth inhibition by NCI-60 assay, while for other CUR–BF 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 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. 3 2 2 2 2 2
  • Digital Object Identifier (doi)

    Author List

  • Laali KK; Zwarycz AT; Bunge SD; Borosky GL; Nukaya M; Kennedy GD
  • Start Page

  • 1173
  • End Page

  • 1184
  • Volume

  • 14
  • Issue

  • 12