Synthesis, solution equilibria and antiproliferative activity of copper(II) aminomethyltriazole and aminomethylthioxotriazoline complexes

The aim of the present study was the synthesis, the determination of formation constants, and the evaluation of the antiproliferative activity of two copper(II) complexes formed with triazole-type ligands. The synthesis of the unsymmetrical triazole ligand 4-amino-3-aminomethyl-5-methyl-1,2,4-triazo...

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Veröffentlicht in:Journal of inorganic biochemistry 2005-08, Vol.99 (8), p.1573-1584
Hauptverfasser: Gaccioli, Francesca, Franchi-Gazzola, Renata, Lanfranchi, Maurizio, Marchiò, Luciano, Metta, Giuseppe, Pellinghelli, Maria Angela, Tardito, Saverio, Tegoni, Matteo
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container_issue 8
container_start_page 1573
container_title Journal of inorganic biochemistry
container_volume 99
creator Gaccioli, Francesca
Franchi-Gazzola, Renata
Lanfranchi, Maurizio
Marchiò, Luciano
Metta, Giuseppe
Pellinghelli, Maria Angela
Tardito, Saverio
Tegoni, Matteo
description The aim of the present study was the synthesis, the determination of formation constants, and the evaluation of the antiproliferative activity of two copper(II) complexes formed with triazole-type ligands. The synthesis of the unsymmetrical triazole ligand 4-amino-3-aminomethyl-5-methyl-1,2,4-triazole (L 1), and its copper(II) complex is reported. The ligand was prepared by functionalization of the carboxylate function of tert-butyloxycarbonyl (BOC) protected glycine O-methyl ester. All intermediates and final products were isolated and characterized with IR, 1H NMR, and elemental analysis. X-ray structures of the ligand as a sulfate salt ((H 2L 1) 2SO 4 · H 2O) and the copper(II) complex [CuCl 2(L 1) 2] are described. The ligand forms a ( N, N) bidentate chelate with the amino group and one triazole nitrogen atom. The tetragonally distorted octahedral coordination of Cu II results from two axially coordinated chloride ions. Protonation constants for L 1 and speciation of the Cu II/L 1 system were determined in 0.1 M aqueous KCl solution at 25 °C. Complexes formed in solution were also characterized by visible spectrophotometry. Ligand substitution competition between L 1 and glycine has also been studied using potentiometric titrations. Antiproliferative activities of ([CuCl 2(L 1) 2]) and [CuCl 2(H 2L 2)]Cl, where HL 2 is the 5-thioxo analog of L 1, against human tumor cell lines HT1080 and HT29 as well as normal human fibroblasts (HF) are presented along with the antiproliferative activities of L 1, CuCl 2, and cisplatin. Activity of these two complexes are discussed and compared with the activity of analogous compounds reported in the literature which contain pyridyl groups in place of the aminomethyl group. In particular, it is suggested that a lypophilic residue such as a pyridyl group is important for antiproliferative activity of this class of compounds.
doi_str_mv 10.1016/j.jinorgbio.2005.04.017
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The synthesis of the unsymmetrical triazole ligand 4-amino-3-aminomethyl-5-methyl-1,2,4-triazole (L 1), and its copper(II) complex is reported. The ligand was prepared by functionalization of the carboxylate function of tert-butyloxycarbonyl (BOC) protected glycine O-methyl ester. All intermediates and final products were isolated and characterized with IR, 1H NMR, and elemental analysis. X-ray structures of the ligand as a sulfate salt ((H 2L 1) 2SO 4 · H 2O) and the copper(II) complex [CuCl 2(L 1) 2] are described. The ligand forms a ( N, N) bidentate chelate with the amino group and one triazole nitrogen atom. The tetragonally distorted octahedral coordination of Cu II results from two axially coordinated chloride ions. Protonation constants for L 1 and speciation of the Cu II/L 1 system were determined in 0.1 M aqueous KCl solution at 25 °C. Complexes formed in solution were also characterized by visible spectrophotometry. Ligand substitution competition between L 1 and glycine has also been studied using potentiometric titrations. Antiproliferative activities of ([CuCl 2(L 1) 2]) and [CuCl 2(H 2L 2)]Cl, where HL 2 is the 5-thioxo analog of L 1, against human tumor cell lines HT1080 and HT29 as well as normal human fibroblasts (HF) are presented along with the antiproliferative activities of L 1, CuCl 2, and cisplatin. Activity of these two complexes are discussed and compared with the activity of analogous compounds reported in the literature which contain pyridyl groups in place of the aminomethyl group. 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The synthesis of the unsymmetrical triazole ligand 4-amino-3-aminomethyl-5-methyl-1,2,4-triazole (L 1), and its copper(II) complex is reported. The ligand was prepared by functionalization of the carboxylate function of tert-butyloxycarbonyl (BOC) protected glycine O-methyl ester. All intermediates and final products were isolated and characterized with IR, 1H NMR, and elemental analysis. X-ray structures of the ligand as a sulfate salt ((H 2L 1) 2SO 4 · H 2O) and the copper(II) complex [CuCl 2(L 1) 2] are described. The ligand forms a ( N, N) bidentate chelate with the amino group and one triazole nitrogen atom. The tetragonally distorted octahedral coordination of Cu II results from two axially coordinated chloride ions. Protonation constants for L 1 and speciation of the Cu II/L 1 system were determined in 0.1 M aqueous KCl solution at 25 °C. Complexes formed in solution were also characterized by visible spectrophotometry. Ligand substitution competition between L 1 and glycine has also been studied using potentiometric titrations. Antiproliferative activities of ([CuCl 2(L 1) 2]) and [CuCl 2(H 2L 2)]Cl, where HL 2 is the 5-thioxo analog of L 1, against human tumor cell lines HT1080 and HT29 as well as normal human fibroblasts (HF) are presented along with the antiproliferative activities of L 1, CuCl 2, and cisplatin. Activity of these two complexes are discussed and compared with the activity of analogous compounds reported in the literature which contain pyridyl groups in place of the aminomethyl group. 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The synthesis of the unsymmetrical triazole ligand 4-amino-3-aminomethyl-5-methyl-1,2,4-triazole (L 1), and its copper(II) complex is reported. The ligand was prepared by functionalization of the carboxylate function of tert-butyloxycarbonyl (BOC) protected glycine O-methyl ester. All intermediates and final products were isolated and characterized with IR, 1H NMR, and elemental analysis. X-ray structures of the ligand as a sulfate salt ((H 2L 1) 2SO 4 · H 2O) and the copper(II) complex [CuCl 2(L 1) 2] are described. The ligand forms a ( N, N) bidentate chelate with the amino group and one triazole nitrogen atom. The tetragonally distorted octahedral coordination of Cu II results from two axially coordinated chloride ions. Protonation constants for L 1 and speciation of the Cu II/L 1 system were determined in 0.1 M aqueous KCl solution at 25 °C. Complexes formed in solution were also characterized by visible spectrophotometry. Ligand substitution competition between L 1 and glycine has also been studied using potentiometric titrations. Antiproliferative activities of ([CuCl 2(L 1) 2]) and [CuCl 2(H 2L 2)]Cl, where HL 2 is the 5-thioxo analog of L 1, against human tumor cell lines HT1080 and HT29 as well as normal human fibroblasts (HF) are presented along with the antiproliferative activities of L 1, CuCl 2, and cisplatin. Activity of these two complexes are discussed and compared with the activity of analogous compounds reported in the literature which contain pyridyl groups in place of the aminomethyl group. In particular, it is suggested that a lypophilic residue such as a pyridyl group is important for antiproliferative activity of this class of compounds.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15953645</pmid><doi>10.1016/j.jinorgbio.2005.04.017</doi><tpages>12</tpages></addata></record>
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subjects Cell Proliferation - drug effects
Cells, Cultured
Chlorides - chemistry
Copper(II)
Crystallography, X-Ray
Cytotoxic/antiproliferative activity
Glycine - chemistry
Humans
Hydrogen-Ion Concentration
Lactones - chemical synthesis
Lactones - chemistry
Lactones - pharmacology
Molecular Structure
Organometallic Compounds - chemical synthesis
Organometallic Compounds - chemistry
Organometallic Compounds - pharmacology
Solubility
Stability constants
Thioxotriazoline
Triazole
Triazoles - chemical synthesis
Triazoles - chemistry
Triazoles - pharmacology
title Synthesis, solution equilibria and antiproliferative activity of copper(II) aminomethyltriazole and aminomethylthioxotriazoline complexes
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