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Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors.

Kim I, Song YH, Singh N, Jeong YJ, Kwon JE, Kim H, Cho YM, Kang SC, Chi KW - Int J Nanomedicine (2015)

Bottom Line: The structure of the representative molecular bowl 5 was confirmed by single-crystal X-ray diffraction analysis.Bowl 6 also induced autophagosome formation via upregulation of p62 and promotion of the conversion of LC3-I to LC3-II.Moreover, bowl 6 promoted apoptotic cell death through downregulation of Akt/mTOR activation, followed by increased caspase-3 activity.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Bio-Resources, Yongin-si, Gyeonggi-Do, Republic of Korea.

ABSTRACT
Nano-sized multinuclear ruthenium complexes have rapidly emerged as promising therapeutic candidates with unique anticancer activities. Here, we describe the coordination-driven self-assembly and anticancer activities of a set of three organometallic tetranuclear Ru(II) molecular bowls. [2+2] Coordination-driven self-assembly of 3, 6-bis(pyridin-3- ylethynyl) phenanthrene (bpep) (1) and one of the three dinuclear arene ruthenium clips, [(η6-p-iPrC6H4Me)2Ru2-(OO\OO)][OTf]2 (OO\OO =2, 5-dioxido-1, 4-benzoquinonato, OTf = triflate) (2), 5, 8-dioxido-1, 4-naphthoquinonato (3), or 6, 11-dioxido-5, 12-naphthacenediona (4), resulted in three molecular bowls 5-7 of general formula [{(η6-p-iPrC6H4Me)2Ru2-(OO\OO)}2(bpep)2][OTf]4. All molecular bowls were obtained as triflate salts in very good yields (>90%) and were fully characterized using multinuclear nuclear magnetic resonance (NMR), electrospray ionization-mass spectrometry (ESI-MS), and elemental analysis. The structure of the representative molecular bowl 5 was confirmed by single-crystal X-ray diffraction analysis. The anticancer activities of molecular bowls 5-7 were determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide, autophagy, and Western blot analysis. Bowl 6 showed the strongest cytotoxicity in AGS human gastric carcinoma cells and was more cytotoxic than doxorubicin. In addition, autophagic activity and the ratio of apoptotic cell death increased in AGS cells by treatment with bowl 6. Bowl 6 also induced autophagosome formation via upregulation of p62 and promotion of the conversion of LC3-I to LC3-II. Moreover, bowl 6 promoted apoptotic cell death through downregulation of Akt/mTOR activation, followed by increased caspase-3 activity. These results suggest that bowl 6 induces gastric cancer cell death via modulation of autophagy and apoptosis. Bowl 6 is a potent anticancer agent and a potential treatment for human gastric cancer that merits further study.

No MeSH data available.


Related in: MedlinePlus

Self-assembly of molecular bowls 5–7.Notes: Molecular bowl 5 was self-assembled using 1 and 2. Molecular bowl 6 was self-assembled using 1 and 3. Molecular bowl 7 was self-assembled using 1 and 4.
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f2-ijn-10-143: Self-assembly of molecular bowls 5–7.Notes: Molecular bowl 5 was self-assembled using 1 and 2. Molecular bowl 6 was self-assembled using 1 and 3. Molecular bowl 7 was self-assembled using 1 and 4.

Mentions: The pure dipyridyl donor 1 was mixed separately with dinuclear Ru(II) p-cymene acceptors 2–4 and solvent CH3NO2/CH3OH (1/1) was added to each resulting mixture. The reaction mixtures were stirred at room temperature for 6 hours to obtain clear solutions. Precipitation and filtration via the addition of diethyl ether yielded 5–7 as analytically pure crystalline powders (Figure 2). The new molecular bowls 5–7 were fully characterized by 1H and 13C NMR, ESI-MS, and elemental analysis. The solid-state structure of complex 5 was determined by single-crystal X-ray analysis.


Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors.

Kim I, Song YH, Singh N, Jeong YJ, Kwon JE, Kim H, Cho YM, Kang SC, Chi KW - Int J Nanomedicine (2015)

Self-assembly of molecular bowls 5–7.Notes: Molecular bowl 5 was self-assembled using 1 and 2. Molecular bowl 6 was self-assembled using 1 and 3. Molecular bowl 7 was self-assembled using 1 and 4.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554412&req=5

f2-ijn-10-143: Self-assembly of molecular bowls 5–7.Notes: Molecular bowl 5 was self-assembled using 1 and 2. Molecular bowl 6 was self-assembled using 1 and 3. Molecular bowl 7 was self-assembled using 1 and 4.
Mentions: The pure dipyridyl donor 1 was mixed separately with dinuclear Ru(II) p-cymene acceptors 2–4 and solvent CH3NO2/CH3OH (1/1) was added to each resulting mixture. The reaction mixtures were stirred at room temperature for 6 hours to obtain clear solutions. Precipitation and filtration via the addition of diethyl ether yielded 5–7 as analytically pure crystalline powders (Figure 2). The new molecular bowls 5–7 were fully characterized by 1H and 13C NMR, ESI-MS, and elemental analysis. The solid-state structure of complex 5 was determined by single-crystal X-ray analysis.

Bottom Line: The structure of the representative molecular bowl 5 was confirmed by single-crystal X-ray diffraction analysis.Bowl 6 also induced autophagosome formation via upregulation of p62 and promotion of the conversion of LC3-I to LC3-II.Moreover, bowl 6 promoted apoptotic cell death through downregulation of Akt/mTOR activation, followed by increased caspase-3 activity.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Bio-Resources, Yongin-si, Gyeonggi-Do, Republic of Korea.

ABSTRACT
Nano-sized multinuclear ruthenium complexes have rapidly emerged as promising therapeutic candidates with unique anticancer activities. Here, we describe the coordination-driven self-assembly and anticancer activities of a set of three organometallic tetranuclear Ru(II) molecular bowls. [2+2] Coordination-driven self-assembly of 3, 6-bis(pyridin-3- ylethynyl) phenanthrene (bpep) (1) and one of the three dinuclear arene ruthenium clips, [(η6-p-iPrC6H4Me)2Ru2-(OO\OO)][OTf]2 (OO\OO =2, 5-dioxido-1, 4-benzoquinonato, OTf = triflate) (2), 5, 8-dioxido-1, 4-naphthoquinonato (3), or 6, 11-dioxido-5, 12-naphthacenediona (4), resulted in three molecular bowls 5-7 of general formula [{(η6-p-iPrC6H4Me)2Ru2-(OO\OO)}2(bpep)2][OTf]4. All molecular bowls were obtained as triflate salts in very good yields (>90%) and were fully characterized using multinuclear nuclear magnetic resonance (NMR), electrospray ionization-mass spectrometry (ESI-MS), and elemental analysis. The structure of the representative molecular bowl 5 was confirmed by single-crystal X-ray diffraction analysis. The anticancer activities of molecular bowls 5-7 were determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide, autophagy, and Western blot analysis. Bowl 6 showed the strongest cytotoxicity in AGS human gastric carcinoma cells and was more cytotoxic than doxorubicin. In addition, autophagic activity and the ratio of apoptotic cell death increased in AGS cells by treatment with bowl 6. Bowl 6 also induced autophagosome formation via upregulation of p62 and promotion of the conversion of LC3-I to LC3-II. Moreover, bowl 6 promoted apoptotic cell death through downregulation of Akt/mTOR activation, followed by increased caspase-3 activity. These results suggest that bowl 6 induces gastric cancer cell death via modulation of autophagy and apoptosis. Bowl 6 is a potent anticancer agent and a potential treatment for human gastric cancer that merits further study.

No MeSH data available.


Related in: MedlinePlus