Synthesis, characterization and cytotoxic activity of gallium(III) complexes anchored by tridentate pyrazole-based ligands

F. Silva, F. Marques, I.C. Santos, A Paulo, A.S. Rodrigues, J. Rueff, I. Santos

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Reactions of GaCl3 with pyrazole-containing ligands of the pyrazole-imine-phenol (HL1-HL3) or pyrazole-amine-phenol (HL4-HL6) types led to the synthesis of well-defined [GaL2](+) homoleptic complexes (1-6). Complexes 1-6 were characterized by elemental analysis, ESI-MS (electrospray ionization-mass spectrometry), IR and NMR spectroscopies, and in the case of Complex 1 also by X-ray diffraction analysis. In complexes 1-3, the pyrazole-imine-phenolate ligands act as monoanionic chelators that coordinate to the metal in a meridional fashion, while 4-6 contain monoanionic and facially coordinated pyrazole-amine-phenolate ligands. Complexes 1-3 have a greater stability in solution compared to 4-6, which have shown a more pronounced tendency to release the respective ancillary ligands. The cytotoxicity of 1-6 and of the respective ligands (HL1-HL6) was evaluated against human prostate cancer cells PC-3 and human breast cancer cells MCF-7. The substituents of the phenolate rings strongly influenced the cytotoxicity of the compounds. Complexes 3 and 6 that contain chloride substituents at the phenolate rings have shown the highest cytotoxicity, including in the cisplatin-resistant PC-3 cell line. The cytotoxic profile of 3 and 6 is very similar to the one displayed by the respective anchor ligands, respectively HL1 and HL6. The cytotoxic activity of 3 and 6 is slightly increased by the presence of transferrin, and both complexes provoke cell death mainly by induction of apoptotic pathways. (C) 2010 Elsevier Inc. All rights reserved.
Original languageUnknown
Pages (from-to)523-532
JournalJournal of Inorganic Biochemistry
Volume104
Issue number5
DOIs
Publication statusPublished - 1 Jan 2010

Keywords

  • Gallium(III) complexes
  • Pyrazole-based ligands
  • X-ray structures
  • Cytotoxicity
  • Apoptosis

Cite this

@article{e17576ba5d0047c691b61b35b7b16120,
title = "Synthesis, characterization and cytotoxic activity of gallium(III) complexes anchored by tridentate pyrazole-based ligands",
abstract = "Reactions of GaCl3 with pyrazole-containing ligands of the pyrazole-imine-phenol (HL1-HL3) or pyrazole-amine-phenol (HL4-HL6) types led to the synthesis of well-defined [GaL2](+) homoleptic complexes (1-6). Complexes 1-6 were characterized by elemental analysis, ESI-MS (electrospray ionization-mass spectrometry), IR and NMR spectroscopies, and in the case of Complex 1 also by X-ray diffraction analysis. In complexes 1-3, the pyrazole-imine-phenolate ligands act as monoanionic chelators that coordinate to the metal in a meridional fashion, while 4-6 contain monoanionic and facially coordinated pyrazole-amine-phenolate ligands. Complexes 1-3 have a greater stability in solution compared to 4-6, which have shown a more pronounced tendency to release the respective ancillary ligands. The cytotoxicity of 1-6 and of the respective ligands (HL1-HL6) was evaluated against human prostate cancer cells PC-3 and human breast cancer cells MCF-7. The substituents of the phenolate rings strongly influenced the cytotoxicity of the compounds. Complexes 3 and 6 that contain chloride substituents at the phenolate rings have shown the highest cytotoxicity, including in the cisplatin-resistant PC-3 cell line. The cytotoxic profile of 3 and 6 is very similar to the one displayed by the respective anchor ligands, respectively HL1 and HL6. The cytotoxic activity of 3 and 6 is slightly increased by the presence of transferrin, and both complexes provoke cell death mainly by induction of apoptotic pathways. (C) 2010 Elsevier Inc. All rights reserved.",
keywords = "ligands, antitumor, ring, structures, Cytotoxicity, inhibition, Gallium(III), Pyrazole-based, in-vitro, iron, X-ray, complexes, Apoptosis, Gallium(III) complexes, Pyrazole-based ligands, X-ray structures, Cytotoxicity, Apoptosis",
author = "F. Silva and F. Marques and I.C. Santos and A Paulo and A.S. Rodrigues and J. Rueff and I. Santos",
note = "WOS:000276274700005",
year = "2010",
month = "1",
day = "1",
doi = "10.1016/j.jinorgbio.2010.01.003",
language = "Unknown",
volume = "104",
pages = "523--532",
journal = "Journal of Inorganic Biochemistry",
issn = "0162-0134",
publisher = "Elsevier Inc.",
number = "5",

}

Synthesis, characterization and cytotoxic activity of gallium(III) complexes anchored by tridentate pyrazole-based ligands. / Silva, F.; Marques, F.; Santos, I.C.; Paulo, A; Rodrigues, A.S.; Rueff, J.; Santos, I.

In: Journal of Inorganic Biochemistry, Vol. 104, No. 5, 01.01.2010, p. 523-532.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthesis, characterization and cytotoxic activity of gallium(III) complexes anchored by tridentate pyrazole-based ligands

AU - Silva, F.

AU - Marques, F.

AU - Santos, I.C.

AU - Paulo, A

AU - Rodrigues, A.S.

AU - Rueff, J.

AU - Santos, I.

N1 - WOS:000276274700005

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Reactions of GaCl3 with pyrazole-containing ligands of the pyrazole-imine-phenol (HL1-HL3) or pyrazole-amine-phenol (HL4-HL6) types led to the synthesis of well-defined [GaL2](+) homoleptic complexes (1-6). Complexes 1-6 were characterized by elemental analysis, ESI-MS (electrospray ionization-mass spectrometry), IR and NMR spectroscopies, and in the case of Complex 1 also by X-ray diffraction analysis. In complexes 1-3, the pyrazole-imine-phenolate ligands act as monoanionic chelators that coordinate to the metal in a meridional fashion, while 4-6 contain monoanionic and facially coordinated pyrazole-amine-phenolate ligands. Complexes 1-3 have a greater stability in solution compared to 4-6, which have shown a more pronounced tendency to release the respective ancillary ligands. The cytotoxicity of 1-6 and of the respective ligands (HL1-HL6) was evaluated against human prostate cancer cells PC-3 and human breast cancer cells MCF-7. The substituents of the phenolate rings strongly influenced the cytotoxicity of the compounds. Complexes 3 and 6 that contain chloride substituents at the phenolate rings have shown the highest cytotoxicity, including in the cisplatin-resistant PC-3 cell line. The cytotoxic profile of 3 and 6 is very similar to the one displayed by the respective anchor ligands, respectively HL1 and HL6. The cytotoxic activity of 3 and 6 is slightly increased by the presence of transferrin, and both complexes provoke cell death mainly by induction of apoptotic pathways. (C) 2010 Elsevier Inc. All rights reserved.

AB - Reactions of GaCl3 with pyrazole-containing ligands of the pyrazole-imine-phenol (HL1-HL3) or pyrazole-amine-phenol (HL4-HL6) types led to the synthesis of well-defined [GaL2](+) homoleptic complexes (1-6). Complexes 1-6 were characterized by elemental analysis, ESI-MS (electrospray ionization-mass spectrometry), IR and NMR spectroscopies, and in the case of Complex 1 also by X-ray diffraction analysis. In complexes 1-3, the pyrazole-imine-phenolate ligands act as monoanionic chelators that coordinate to the metal in a meridional fashion, while 4-6 contain monoanionic and facially coordinated pyrazole-amine-phenolate ligands. Complexes 1-3 have a greater stability in solution compared to 4-6, which have shown a more pronounced tendency to release the respective ancillary ligands. The cytotoxicity of 1-6 and of the respective ligands (HL1-HL6) was evaluated against human prostate cancer cells PC-3 and human breast cancer cells MCF-7. The substituents of the phenolate rings strongly influenced the cytotoxicity of the compounds. Complexes 3 and 6 that contain chloride substituents at the phenolate rings have shown the highest cytotoxicity, including in the cisplatin-resistant PC-3 cell line. The cytotoxic profile of 3 and 6 is very similar to the one displayed by the respective anchor ligands, respectively HL1 and HL6. The cytotoxic activity of 3 and 6 is slightly increased by the presence of transferrin, and both complexes provoke cell death mainly by induction of apoptotic pathways. (C) 2010 Elsevier Inc. All rights reserved.

KW - ligands

KW - antitumor

KW - ring

KW - structures

KW - Cytotoxicity

KW - inhibition

KW - Gallium(III)

KW - Pyrazole-based

KW - in-vitro

KW - iron

KW - X-ray

KW - complexes

KW - Apoptosis

KW - Gallium(III) complexes

KW - Pyrazole-based ligands

KW - X-ray structures

KW - Cytotoxicity

KW - Apoptosis

U2 - 10.1016/j.jinorgbio.2010.01.003

DO - 10.1016/j.jinorgbio.2010.01.003

M3 - Article

VL - 104

SP - 523

EP - 532

JO - Journal of Inorganic Biochemistry

JF - Journal of Inorganic Biochemistry

SN - 0162-0134

IS - 5

ER -