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. 2019 Feb 13:2019:2069250.
doi: 10.1155/2019/2069250. eCollection 2019.

Synthesis and Characterization of 3-(1-((3,4-Dihydroxyphenethyl)amino)ethylidene)-chroman-2,4-dione as a Potential Antitumor Agent

Dušan S Dimić  1 , Zoran S Marković  2 , Luciano Saso  3 , Edina H Avdović  4 , Jelena R Đorović  5 , Isidora P Petrović  6 , Danijela D Stanisavljević  6 , Milena J Stevanović  6   7   8 , Ivan Potočňák  9 , Erika Samoľová  9 , Srećko R Trifunović  4 , Jasmina M Dimitrić Marković  1
Affiliations

Synthesis and Characterization of 3-(1-((3,4-Dihydroxyphenethyl)amino)ethylidene)-chroman-2,4-dione as a Potential Antitumor Agent

Dušan S Dimić et al. Oxid Med Cell Longev. .

Abstract

The newly synthesized coumarin derivative with dopamine, 3-(1-((3,4-dihydroxyphenethyl)amino)ethylidene)-chroman-2,4-dione, was completely structurally characterized by X-ray crystallography. It was shown that several types of hydrogen bonds are present, which additionally stabilize the structure. The compound was tested in vitro against different cell lines, healthy human keratinocyte HaCaT, cervical squamous cell carcinoma SiHa, breast carcinoma MCF7, and hepatocellular carcinoma HepG2. Compared to control, the new derivate showed a stronger effect on both healthy and carcinoma cell lines, with the most prominent effect on the breast carcinoma MCF7 cell line. The molecular docking study, obtained for ten different conformations of the new compound, showed its inhibitory nature against CDKS protein. Lower inhibition constant, relative to one of 4-OH-coumarine, proved stronger and more numerous interactions with CDKS protein. These interactions were carefully examined for both parent molecule and derivative and explained from a structural point of view.

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Figures

Scheme 1
Scheme 1
Synthesis of 3-(1-((3,4-dihydroxyphenethyl)amino)ethylidene)-chroman-2,4-dione.
Figure 1
Figure 1
Molecular structure with an atom numbering scheme of 3·MeOH. Displacement ellipsoids are drawn at 50% probability; hydrogen bonds are shown as red dashed lines.
Figure 2
Figure 2
Molecular packing of 3·MeOH showing π-π interactions (black dashed lines) between neighboring chains formed by hydrogen bonds (red dashed lines). Hydrogen atoms not involved in hydrogen bonds are omitted for clarity.
Figure 3
Figure 3
Cell viability assay (MTS assay) on HaCaT, SiHa, MCF7, and HepG2 cells performed 48 h after treatment with either 4-OH-coumarin or compound 3. Relative cell viability of cells treated with selected compounds was calculated as a percentage of DMSO-treated cell viability that was set as 100%. Data are presented as the means ± S.E.M. (standard error mean) of at least three independent experiments performed in triplicate for each concentration. Mean values of relative cell viability were compared with Student's t-test, and p values are presented as ∗ p ≤ 0.05, ∗∗ p ≤ 0.01, and ∗∗∗ p ≤ 0.001. Each color corresponds to a bar presented on the histogram.)
Figure 4
Figure 4
Docking positions of 4-OH-coumarin.
Figure 5
Figure 5
Docking positions of coumarin derivate.
See this image and copyright information in PMC

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