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

Abstract

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 retro-curcuminoids (7–14), was synthesized and characterized using 1D 1H- and 13C-NMR, IR, and mass spectrometry; the X-ray structure of 7, 8, 9, 10, 12, 13, and 14 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 7, 8, 9, and 10 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 7 and 10. Compounds 7, 8, and 10 showed relevant cytotoxic activity against these cancer cell lines, and 10 showed a protective effect against lipid peroxidation. The molecular resemblance to curcuminoids and analogs with ortho substituents suggests a potential source of useful bioactive compounds.

Synthesis, Anti-inflammatory, and Antioxidant Activity of Mannich Bases of Dehydrozingerone Derivatives

“…Like as curcumin, the compound also exhibits a wide range of biological activities such as anti-inflammatory, antioxidant, antimicrobial, and cytotoxic activity. [1][2][3][4][5][6][7][8] Various chemical modification of DHZ has been performed to exploit for diverse biological activities of DHZ derivatives, such as esterification or alkylation of OH phenolic group, replacement of OH with other substituents, substitution of the methoxy group, reduction of double bond, cyclization of α,β-unsaturated carbonyl, and substitution of hydrogen atom bound to the carbonyl α-carbon. 2,4,[9][10][11] Some Mannich bases of DHZ have been synthesized and reported to have better anti-inflammatory activity compared to DHZ and fairly good anti-inflammatory activity compared to indomethacin.…”

The Multi‐Biological Targeted Role of Dehydrozingerone and its Analogues

“…Mendoza et al presented a library of DZG-based compounds that were evaluated for cytotoxicity against the human cancer cell lines K562, MCF-7, and SKLU-1. [52] Compound 74 (Figure 12) exhibited significant anticancer activity (IC 50 values of 8.6, 12.01, and 8.07 μM, respectively), comparable to curcumin. Additionally, the lipid peroxidation study on the rat brain research determined that 74 had a preventive role against lipid peroxidation, with an inhibition value of (96.18 %) at a 50 μg/ml dose.…”

“…Mendoza et al . presented a library of DZG‐based compounds that were evaluated for cytotoxicity against the human cancer cell lines K562, MCF‐7, and SKLU‐1 [52] . Compound 74 (Figure 12) exhibited significant anticancer activity (IC 50 values of 8.6, 12.01, and 8.07 μM, respectively), comparable to curcumin.…”

Tailored Functionalization of Natural Phenols to Improve Biological Activity

“…A family of compounds, named by the authors retro-curcuminoids, was prepared maintaining only “half” of the curcumin structure ( Scheme 50 ), because the β -dicarbonyl moiety was considered responsible for curcumin scarce stability [ 448 ]. Resulting compounds showed relevant cytotoxic activity against human cancer cell lines, but they did not injure healthy cells.…”