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Investigation of the biological and anti-cancer properties of ellagic acid-encapsulated nano-sized metalla-cages.

Dubey A, Park DW, Kwon JE, Jeong YJ, Kim T, Kim I, Kang SC, Chi KW - Int J Nanomedicine (2015)

Bottom Line: Compounds 9 and 10 showed potent antioxidant activity, but 10 had the superior ORACPE value (1.30 ± 0.020).In a tumoricidal assay, ellagic acid (5) and compound 10 induced cytotoxicity in tumor cells, while doxorubicin did not.While free ellagic acid had no effect on the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein, the encapsulated metalla-prism 10 stimulated granulocyte-colony stimulating factor and reduced regulated on activation normal T cell expressed and secreted protein expression in the RAW264.7 macrophage line.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Ulsan, Ulsan, Republic of Korea.

ABSTRACT
Three new large hexanuclear metalla-prisms 9-11 incorporating 1,3, 5-tris(pyridin-4-ylethynyl)benzene (tpeb) 4 and one of the dinuclear arene ruthenium clips [Ru2(p-iPrC6H4Me)2(OO∩OO)][CF3SO3]2 (OO∩OO =2,5-dioxydo-1,4-benzoquinonato [dobq] 1, 5,8-dihydroxy-1,4-naphthaquinonato (donq) 2, and 6,11-dihydroxy-5,12-naphthacenedionato [dotq] 3), which encapsulate the guest molecule ellagic acid (2,3,7,8-tetrahydroxy-chromeno[5,4,3-cde]chromene-5,10-dione, 5) were prepared. All complexes were isolated as triflate salts in good yields and were fully characterized by (1)H NMR spectroscopy and electrospray ionization mass spectrometry. The photophysical properties of these metalla-prisms were also investigated. Compounds 9 and 10 showed potent antioxidant activity, but 10 had the superior ORACPE value (1.30 ± 0.020). Ellagic acid (5) and compound 11 showed weaker activity than that of Trolox. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the metalla-prism compounds exhibit anticancer properties in vitro. Compound 10 inhibited the growth of all cancer cell lines at micromolar concentrations, with the highest cytotoxicity observed against A549 human lung cancer cells (IC50 =25.9 μM). However, these compounds had a lower anti-cancer activity than that of doxorubicin. In a tumoricidal assay, ellagic acid (5) and compound 10 induced cytotoxicity in tumor cells, while doxorubicin did not. While free ellagic acid had no effect on the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein, the encapsulated metalla-prism 10 stimulated granulocyte-colony stimulating factor and reduced regulated on activation normal T cell expressed and secreted protein expression in the RAW264.7 macrophage line. Our results show that ellagic acid encapsulated in metalla-prisms inhibited cancer cells via the modulation of mRNA induction and protein expression levels of the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein in macrophages.

No MeSH data available.


Related in: MedlinePlus

Excerpts of 1H NMR spectra of (A) ellagic acid (5), (B) empty prism 6, (C) encapsulated prism 9, (D) empty prism 7, (E) encapsulated prism 10, (F) empty prism 8 and (G) encapsulated prism 11 in CD3NO2:CD3OD (1:1) solution.Abbreviation: ppm, parts per million.
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f2-ijn-10-227: Excerpts of 1H NMR spectra of (A) ellagic acid (5), (B) empty prism 6, (C) encapsulated prism 9, (D) empty prism 7, (E) encapsulated prism 10, (F) empty prism 8 and (G) encapsulated prism 11 in CD3NO2:CD3OD (1:1) solution.Abbreviation: ppm, parts per million.

Mentions: The formation of the compounds 9–11 was monitored by 1H NMR spectroscopy in CD3NO2:CD3OD solution (1:1, Figure 2). The resonance of the ellagic acid proton was observed to be shifted upfield upon formation of the encapsulated system compounds 9–11. Similarly, in the 1H NMR spectra of 9–11, the signals corresponding to the Hα and Hβ nuclei of the pyridine rings were observed to undergo upfield shifts (Δδ =0.2–0.3 ppm) relative to 4, indicative of the metal pyridine coordination. Protons of the ligand panel in 9–11 were shifted upfield in comparison with the empty cages 6–8. The signals of the CH protons of the dobq, donq, and dotq bridging ligands remained almost unchanged. The proton resonances of the p-cymene ligands located at the periphery of the prism were not significantly affected by the presence of ellagic acid (5) in the cavities of 9–11.


Investigation of the biological and anti-cancer properties of ellagic acid-encapsulated nano-sized metalla-cages.

Dubey A, Park DW, Kwon JE, Jeong YJ, Kim T, Kim I, Kang SC, Chi KW - Int J Nanomedicine (2015)

Excerpts of 1H NMR spectra of (A) ellagic acid (5), (B) empty prism 6, (C) encapsulated prism 9, (D) empty prism 7, (E) encapsulated prism 10, (F) empty prism 8 and (G) encapsulated prism 11 in CD3NO2:CD3OD (1:1) solution.Abbreviation: ppm, parts per million.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562765&req=5

f2-ijn-10-227: Excerpts of 1H NMR spectra of (A) ellagic acid (5), (B) empty prism 6, (C) encapsulated prism 9, (D) empty prism 7, (E) encapsulated prism 10, (F) empty prism 8 and (G) encapsulated prism 11 in CD3NO2:CD3OD (1:1) solution.Abbreviation: ppm, parts per million.
Mentions: The formation of the compounds 9–11 was monitored by 1H NMR spectroscopy in CD3NO2:CD3OD solution (1:1, Figure 2). The resonance of the ellagic acid proton was observed to be shifted upfield upon formation of the encapsulated system compounds 9–11. Similarly, in the 1H NMR spectra of 9–11, the signals corresponding to the Hα and Hβ nuclei of the pyridine rings were observed to undergo upfield shifts (Δδ =0.2–0.3 ppm) relative to 4, indicative of the metal pyridine coordination. Protons of the ligand panel in 9–11 were shifted upfield in comparison with the empty cages 6–8. The signals of the CH protons of the dobq, donq, and dotq bridging ligands remained almost unchanged. The proton resonances of the p-cymene ligands located at the periphery of the prism were not significantly affected by the presence of ellagic acid (5) in the cavities of 9–11.

Bottom Line: Compounds 9 and 10 showed potent antioxidant activity, but 10 had the superior ORACPE value (1.30 ± 0.020).In a tumoricidal assay, ellagic acid (5) and compound 10 induced cytotoxicity in tumor cells, while doxorubicin did not.While free ellagic acid had no effect on the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein, the encapsulated metalla-prism 10 stimulated granulocyte-colony stimulating factor and reduced regulated on activation normal T cell expressed and secreted protein expression in the RAW264.7 macrophage line.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Ulsan, Ulsan, Republic of Korea.

ABSTRACT
Three new large hexanuclear metalla-prisms 9-11 incorporating 1,3, 5-tris(pyridin-4-ylethynyl)benzene (tpeb) 4 and one of the dinuclear arene ruthenium clips [Ru2(p-iPrC6H4Me)2(OO∩OO)][CF3SO3]2 (OO∩OO =2,5-dioxydo-1,4-benzoquinonato [dobq] 1, 5,8-dihydroxy-1,4-naphthaquinonato (donq) 2, and 6,11-dihydroxy-5,12-naphthacenedionato [dotq] 3), which encapsulate the guest molecule ellagic acid (2,3,7,8-tetrahydroxy-chromeno[5,4,3-cde]chromene-5,10-dione, 5) were prepared. All complexes were isolated as triflate salts in good yields and were fully characterized by (1)H NMR spectroscopy and electrospray ionization mass spectrometry. The photophysical properties of these metalla-prisms were also investigated. Compounds 9 and 10 showed potent antioxidant activity, but 10 had the superior ORACPE value (1.30 ± 0.020). Ellagic acid (5) and compound 11 showed weaker activity than that of Trolox. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the metalla-prism compounds exhibit anticancer properties in vitro. Compound 10 inhibited the growth of all cancer cell lines at micromolar concentrations, with the highest cytotoxicity observed against A549 human lung cancer cells (IC50 =25.9 μM). However, these compounds had a lower anti-cancer activity than that of doxorubicin. In a tumoricidal assay, ellagic acid (5) and compound 10 induced cytotoxicity in tumor cells, while doxorubicin did not. While free ellagic acid had no effect on the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein, the encapsulated metalla-prism 10 stimulated granulocyte-colony stimulating factor and reduced regulated on activation normal T cell expressed and secreted protein expression in the RAW264.7 macrophage line. Our results show that ellagic acid encapsulated in metalla-prisms inhibited cancer cells via the modulation of mRNA induction and protein expression levels of the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein in macrophages.

No MeSH data available.


Related in: MedlinePlus