Retro-Curcuminoids as Mimics of Dehydrozingerone and Curcumin: Synthesis, NMR, X-ray, and Cytotoxic Activity.

Curcumin and its derivatives have been extensively studied for their remarkable medicinal properties, and their chemical synthesis has been an important step in the optimization of well-controlled laboratory production. A family of new compounds that mimic the structure of curcumin and curcuminoids, here named -curcuminoids (-), was synthesized and characterized using 1D ¹H- and C-NMR, IR, and mass spectrometry; the X-ray structure of , , , , , , and are reported here for the first time. The main structural feature of these compounds is the reverse linkage of the two aromatic moieties, where the acid chloride moiety is linked to the phenolic group while preserving α, β-unsaturated ketone functionality. The cytotoxic screening of , , , and at 50 and 10 µg/mL was carried out with human cancer cell lines K562, MCF-7, and SKLU-1. Lipid peroxidation on rat brain was also tested for compounds and . Compounds , , and showed relevant cytotoxic activity against these cancer cell lines, and showed a protective effect against lipid peroxidation. The molecular resemblance to curcuminoids and analogs with substituents suggests a potential source of useful bioactive compounds.