174138-01-3Relevant articles and documents
DNA damage and induction of apoptosis in pancreatic cancer cells by a new dinuclear bis(triazacyclonane) copper complex
Montagner, Diego,Gandin, Valentina,Marzano, Cristina,Erxleben, Andrea
, p. 101 - 107 (2015)
The dinuclear copper(II) complex [Cu2{bcmp(-H)}(μ-OH)](NO3)2·H2O (1, bcmp = 2,6-bis(1,4,7-triazacyclonon-1-ylmethyl)-4-methylphenol) has been synthesized and characterized by electrospray ionization mass spectrometry, potentiometric titration and cyclovoltammetry. The X-ray structure of the analogous perchlorate salt [Cu2{bcmp(-H)}(μ-OH)](ClO4)2·2.5H2O (2) was determined. Cytotoxicity studies showed very promising activity of 1 against various pancreatic tumor cell lines with IC50 values comparable or even lower than those of cisplatin. The Cu complex displayed low toxicity against a human non-tumor cell line (HEK 293) demonstrating selectivity for cancer cells. 1 converts supercoiled pUC19 plasmid DNA into the nicked form at micromolar concentrations in the absence of added reductants. A detailed kinetic study on the hydrolysis of the DNA model bis(2,4-dinitrophenyl) phosphate (BDNPP) has been performed. 1 hydrolyses BDNPP with a second order rate constant of 0.047 M s- 1 at pH 8 and 40 °C. Finally, single cell electrophoresis (comet assay) and fluorescence microscopy analysis showed that 1 interacts with cellular DNA and induces apoptotic cell death of Capan-1 pancreatic cancer cells. Western blotting analysis indicated that the Cu complex activates the p53 dependent pathway of apoptosis.
Phototoxic activity and DNA interactions of water-soluble porphyrins and their rhenium(I) conjugates
Mion, Giuliana,Gianferrara, Teresa,Bergamo, Alberta,Gasser, Gilles,Pierroz, Vanessa,Rubbiani, Riccardo,Vilar, Ramon,Leczkowska, Anna,Alessio, Enzo
, p. 1901 - 1914 (2015)
In the search for alternative photosensitizers for use in photodynamic therapy (PDT), herein we describe two new water-soluble porphyrins, a neutral fourfold-symmetric compound and a +3-charged tris-methylpyridinium derivative, in which either four or one
TACN-based cationic lipids with amino acid backbone and double tails: Materials for non-viral gene delivery
Wang, Bing,Yi, Wen-Jing,Zhang, Ji,Zhang, Qin-Fang,Xun, Miao-Miao,Yu, Xiao-Qi
, p. 1771 - 1775 (2014)
Cationic lipids have become an efficient type of non-viral vectors for gene delivery. In this Letter, four cationic lipids containing 1,4,7- triazacyclononane (TACN) headgroup, glutamic/aspartic acid backbone and dioleyl tails were designed and synthesize
Self-Assembled Multivalent Ag-SR Coordination Polymers with Phosphatase-Like Activity
Cao, Ying-Juan,Yao, Mei-Xia,Prins, Leonard J.,Ji, Rui-Xue,Liu, Ning,Sun, Xiang-Ying,Jiang, Yun-Bao,Shen, Jiang-Shan
, p. 7646 - 7650 (2021)
We show herein the phosphatase-like catalytic activity of coordination polymers obtained after adding Ag+-ions to thiols bearing hydrophobic alkyl chains terminated with a 1,4,7-triazacyclononane (TACN) group. The subsequent addition of Zn2+ -ions to the self-assembled polymers resulted in the formation of multivalent metal coordination polymers capable of catalysing the transphosphorylation of an RNA-model compound (2-hydroxypropyl-4-nitrophenyl phosphate, HPNPP) with high reactivity. Analysis of a series of metal ions showed that the highest catalytic activity was obtained when Ag+-ions were used as the first metal ions to construct the backbone of the coordination polymer through interaction with the -SH group followed by Zn2+-ions as the second metal ions complexed by the TACN-macrocycle. Furthermore, it was demonstrated that the catalytic activity could be modulated by changing the length of the hydrophobic alkyl chain.
Synthesis and evaluation of novel 1,4,7-triazacyclononane derivatives as Cu2+ and Ga3+ chelators
Wang, Sheng,Gai, Yongkang,Sun, Lingyi,Lan, Xiaoli,Zeng, Dexing,Xiang, Guangya,Ma, Xiang
, (2022/01/24)
Advances in chelator design are the cornerstone for the development of metals like copper and gallium based biomedical agents and radiopharmaceuticals. To develop optimal chelating ligands, we explored the synthesis and chelating properties of azaheterocycle pendant armed 1,4,7-triazacyclononane (TACN) dimethylcarboxylate derivatives and dimethylphosphonate derivatives. In the complexation kinetics test, dicarboxylate pendant armed TACN derivatives 2,2′-(7-((1H-imidazol-2-yl)methyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NODA-Im), 2,2′-(7-((1-methyl-1H-imidazol-2-yl)methyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NODA-MeIm), and 2,2′-(7-(thiazol-2-ylmethyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NODA-Thia) exhibited fast complexation kinetics towards Cu (II) cations, which were comparable to the frequently explored ligand 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). And the diphosphonate pendant armed TACN derivative ((7-(thiazol-2-ylmethyl)-1,4,7-triazonane-1,4-diyl)bis(methylene))bis(phosphonic acid) (NODP-Thia) bound with Ga (III) cations at a much faster rate than NOTA. Density functional theory studies confirmed that the better complexation kinetics and metal chelating efficiency of NODA-Im, NODA-MeIm, NODA-Thia, and NODP-Thia could be ascribed to the lower Gibbs energies of corresponding chelator-metal complexes than NOTA-metal complexes. The kinetic inertness of the Cu (II) complex with NODA-Im, NODA-MeIm, and NODA-Thia was also demonstrated by cyclic voltammetry studies. Subsequently radiolabeling experiment demonstrated that these metal chelators could efficiently labeled with 64Cu or 68Ga in good radiochemical purities. These preliminary findings support NODA-Im, NODA-MeIm, NODA-Thia, and NODP-Thia as promising leading chelating agents for the development of bifunctional Cu2+ and Ga3+ chelators in biomedical applications.
Design, Synthesis, and Biological Evaluation of Boron-Containing Macrocyclic Polyamines and Their Zinc(II) Complexes for Boron Neutron Capture Therapy
Ueda, Hiroki,Suzuki, Minoru,Kuroda, Reiko,Tanaka, Tomohiro,Aoki, Shin
, p. 8523 - 8544 (2021/06/28)
Boron neutron capture therapy (BNCT) is a binary therapeutic method for cancer treatment based on the use of a combination of a cancer-specific drug containing boron-10 (10B) and thermal neutron irradiation. For successful BNCT,10B-containing molecules need to accumulate specifically in cancer cells, because destructive effect of the generated heavy particles is limited basically to boron-containing cells. Herein, we report on the design and synthesis of boron compounds that are functionalized with 9-, 12-, and 15-membered macrocyclic polyamines and their Zn2+complexes. Their cytotoxicity, intracellular uptake activity into cancer cells and normal cells, and BNCT effect are also reported. The experimental data suggest that mono- and/or diprotonated forms of metal-free [12]aneN4- and [15]aneN5-type ligands are uptaken into cancer cells, and their complexes with intracellular metals such as Zn2+would induce cell death upon thermal neutron irradiation, possibly via interactions with DNA.
