Anticancer Potency and Multidrug‐Resistant Studies of Self‐Assembled Arene–Ruthenium Metallarectangles

Abstract

A suite of three tetraruthenium metallacycles have been obtained from [2+2] self-assemblies between N,N'-Di-(4-pyridyl)-1,4,5,8-naphthalenetetracarbo-xydiimide (4) and one of the three dinuclear arene ruthenium clips, (η(6)-p-iPrC6H4Me)2Ru2(OO∩OO)][OTf]2 (OO∩OO = oxalate 1, 2,5-dioxydo-1,4-benzoquinonato (dobq) 2, 5,8-dihydroxy-1,4-naphthaquinonato (donq) 3; OTf = triflate). All complexes were isolated in good yield (>85 %) as triflate salts and were fully characterized by using (1)H NMR and UV/Vis spectroscopies, and high-resolution electrospray mass spectrometry. A single crystal of the metallarectangle 5 was suitable for X-ray diffraction structural characterization. The biological activities of the metallacycles were determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays, establishing their in vitro anticancer properties. Our results show that for the AGC (gastric cancer) cell lines, the cytotoxicity of (donq)-containing SCC 7 exceeds that of cisplatin, which was used as a control. For HCT15 (colon cancer) cell lines, the cytotoxicity is comparable to both cisplatin and doxorubicin. An in vivo hollow fiber model was used to show growth-inhibitory activity against HCT15 and image-based cytometry experiments indicated that 7 induced apoptosis as the mode of cell death. Complex 7 also showed significant antitumor activity for multidrug-resistant HCT15/CLO2 cell lines, for which doxorubicin was ineffective.

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

“…Because inhibition of the Akt/ mTOR pathway is associated with inhibition of autophagy in cancer cells, potential anticancer agents can maintain tumor survival or induce tumor growth. 12,[41][42][43] Expression of p-Akt in the bowl 6-treated AGS cells significantly decreased in comparison with that in the untreated cells, which was in accordance with the downregulation of mTOR in comparison with the untreated cells ( Figure 6B). To assess whether bowl 6 induced caspase-mediated apoptosis, caspase-3 activity was measured using a substrate cleavage-based assay.…”

“…[1][2][3][4][5][6] Thus, a growing number of Ru(II)-based, self-assembled large two-dimensional and three-dimensional architectures have been developed which have shown promising results in human cancer cell lines as antitumor agents. [7][8][9][10][11][12][13][14] Therrien and others exploited the self-assembly approach to design finite, nano-sized molecular architectures by combining organometallic halfsandwich acceptor clips and pyridyl-based donors. [15][16][17][18] Nanostructures based on halfsandwich arene-ruthenium complexes are promising candidates for cancer treatments, as they possess advantageous features such as low toxicity and a balance of hydrophilicity and hydrophobicity, a key issue for their transport in biological media.…”

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

“…[10][11][12][13][14][15][16][17][18][19] Three-dimensional cages, engineered via coordinationdriven self-assembly paradigms, have distinct advantages over conventional covalentcontainer molecules, owing to the synthetic ease with which the coordination cages can be assembled, the availability of a large library of building blocks, and the ability to design selective guest encapsulations. 20,21 The strong and highly directional nature of metal-ligand interactions results in the formation of stable and rigid coordination…”

Spotlight on nano-theranostics in South Korea: applications in diagnostics and treatment of diseases

“…To address these new challenges, scientists in Gyeonggi-do, South Korea, have recently been developing new types of silica-based CAs and anticancer delivery vehicles. 5 antibacterial agents and neurodegenerative testing…”

“…Interestingly, the multifunctional nanoparticles showed enhanced magnetic resonance relaxivity compared to previously reported materials. Kim et al and Dubey et al investigated the anticancer properties of self-assembled molecular bowls containing phenanthrene-based donor 5 and RU(II) acceptors and ellagic acid encapsulated nanosize metalla. Molecular bowel 6 was selectively cytotoxic to gastric cancer cells in the first paper, whereas ellagic acid metalla (compound 10) exhibited an inhibitory effect for cancer via granulocyte-colony stimulating factor (G-CSF) induction and Rantes inhibition in the second one.…”