Neutron activation of In(iii) complexes with thiosemicarbazones leads to the production of potential radiopharmaceuticals for the treatment of breast cancerElectronic supplementary information (ESI) available: FT-IR spectra of ligand H2Ac4oClPh and complex (1), as well as their 1H and 13C{1H} NMR spectra together with the 2D COSY, HMQC and HMBC contour maps used to support the 1H and 13C attributions; X-ray crystallography data and the high resolution mass spectra [ESI(+), IT-TOF] of 1 and 2; an
In( iii ) complexes [In(2Ac4 o ClPh) 2 ]NO 3 ( 1 ) and [In(2Ac4 p FPh) 2 ]NO 3 ·1.5H 2 O ( 2 ) were obtained with N (4)- ortho -chlorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4 o ClPh) and N (4)- para -fluorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4 p FPh). Neutron activation of complex...
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Format | Journal Article |
Language | English |
Published |
21.08.2017
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Abstract | In(
iii
) complexes [In(2Ac4
o
ClPh)
2
]NO
3
(
1
) and [In(2Ac4
p
FPh)
2
]NO
3
·1.5H
2
O (
2
) were obtained with
N
(4)-
ortho
-chlorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4
o
ClPh) and
N
(4)-
para
-fluorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4
p
FPh). Neutron activation of complexes (
1
) and (
2
), and of previously prepared [In(2Ac4
o
ClPh)Cl
2
(MeOH)] (
3
) and [In(2Ac4
p
FPh)Cl
2
(MeOH)] (
4
) resulted in the formation of
114m
In/
115m
In analogues (
*1-*4
). The cytotoxic activities of the compounds under study were investigated on MCF-7 breast cancer cells as well as against non-malignant MRC-5 fibroblast cells. Upon coordination to In(
iii
) the cytotoxicity against MCF-7 cells significantly increased in complexes (
1-4
), suggesting that complexation was a good strategy to improve the cytotoxic effect. While both non-radioactive and radioactive In(
iii
) salts were inactive against MCF-7 cells, the radioactive complexes (
*1-*4
) proved to be 10
2
to 10
4
times more potent than the non-radioactive analogues (
1-4
). For the non-radioactive In(
iii
) complexes (
1-4
) the selectivity indexes (SI), defined as IC
50 MRC-5
/IC
50 MCF-7
, were SI = 0.07-0.36, while high values of SI were found for the radioactive In(
iii
) analogues (
*1-*4
), SI = 46-4716, indicating that irradiation represented an interesting strategy for increasing the selectivity. Since cytotoxicity was evaluated following 48 h of treatment and 72 h after neutron activation, the observed cytotoxic effects were attributed mainly to
114m
In, the contribution of the
115m
In (
t
1/2
= 4.5 h) isomer being considered irrelevant. Complexes (
*1-*4
) induced higher levels of intracellular ROS in MCF-7 cells in comparison to the parent compounds. The results suggest that
114m
In complexes with thiosemicarbazones might show potential for application as radiopharmaceuticals for the treatment of breast cancer.
114m
In(
iii
) complexes with 2-acetylpyridine-derived thiosemicarbazones show potent cytotoxic activity. |
---|---|
AbstractList | In(
iii
) complexes [In(2Ac4
o
ClPh)
2
]NO
3
(
1
) and [In(2Ac4
p
FPh)
2
]NO
3
·1.5H
2
O (
2
) were obtained with
N
(4)-
ortho
-chlorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4
o
ClPh) and
N
(4)-
para
-fluorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4
p
FPh). Neutron activation of complexes (
1
) and (
2
), and of previously prepared [In(2Ac4
o
ClPh)Cl
2
(MeOH)] (
3
) and [In(2Ac4
p
FPh)Cl
2
(MeOH)] (
4
) resulted in the formation of
114m
In/
115m
In analogues (
*1-*4
). The cytotoxic activities of the compounds under study were investigated on MCF-7 breast cancer cells as well as against non-malignant MRC-5 fibroblast cells. Upon coordination to In(
iii
) the cytotoxicity against MCF-7 cells significantly increased in complexes (
1-4
), suggesting that complexation was a good strategy to improve the cytotoxic effect. While both non-radioactive and radioactive In(
iii
) salts were inactive against MCF-7 cells, the radioactive complexes (
*1-*4
) proved to be 10
2
to 10
4
times more potent than the non-radioactive analogues (
1-4
). For the non-radioactive In(
iii
) complexes (
1-4
) the selectivity indexes (SI), defined as IC
50 MRC-5
/IC
50 MCF-7
, were SI = 0.07-0.36, while high values of SI were found for the radioactive In(
iii
) analogues (
*1-*4
), SI = 46-4716, indicating that irradiation represented an interesting strategy for increasing the selectivity. Since cytotoxicity was evaluated following 48 h of treatment and 72 h after neutron activation, the observed cytotoxic effects were attributed mainly to
114m
In, the contribution of the
115m
In (
t
1/2
= 4.5 h) isomer being considered irrelevant. Complexes (
*1-*4
) induced higher levels of intracellular ROS in MCF-7 cells in comparison to the parent compounds. The results suggest that
114m
In complexes with thiosemicarbazones might show potential for application as radiopharmaceuticals for the treatment of breast cancer.
114m
In(
iii
) complexes with 2-acetylpyridine-derived thiosemicarbazones show potent cytotoxic activity. |
Author | Oliveira, Alexandre A da Silva, Jeferson G dos Santos, Raquel G Souza-Fagundes, Elaine M Beraldo, Heloisa Perdigão, Gabriele M. C Franco, Lucas L |
AuthorAffiliation | Universidade Federal de Minas Gerais CDTN Departamento de Farmácia Universidade Federal de Juiz de Fora Centro de Desenvolvimento da Tecnologia Nuclear Campus Governador Valadares Departamento de Fisiologia e Biofísica Departamento de Química |
AuthorAffiliation_xml | – name: Universidade Federal de Minas Gerais – name: Centro de Desenvolvimento da Tecnologia Nuclear – name: Departamento de Farmácia – name: CDTN – name: Universidade Federal de Juiz de Fora – name: Campus Governador Valadares – name: Departamento de Fisiologia e Biofísica – name: Departamento de Química |
Author_xml | – sequence: 1 givenname: Alexandre A surname: Oliveira fullname: Oliveira, Alexandre A – sequence: 2 givenname: Lucas L surname: Franco fullname: Franco, Lucas L – sequence: 3 givenname: Raquel G surname: dos Santos fullname: dos Santos, Raquel G – sequence: 4 givenname: Gabriele M. C surname: Perdigão fullname: Perdigão, Gabriele M. C – sequence: 5 givenname: Jeferson G surname: da Silva fullname: da Silva, Jeferson G – sequence: 6 givenname: Elaine M surname: Souza-Fagundes fullname: Souza-Fagundes, Elaine M – sequence: 7 givenname: Heloisa surname: Beraldo fullname: Beraldo, Heloisa |
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ContentType | Journal Article |
DOI | 10.1039/c7nj01547j |
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Notes | 13 C 1544503 10.1039/c7nj01547j ( C attributions; X-ray crystallography data and the high resolution mass spectra [ESI(+), IT-TOF] of o as well as their 1a 1 H} NMR spectra together with the 2D COSY, HMQC and HMBC contour maps used to support the For ESI and crystallographic data in CIF or other electronic format see DOI ClPh and complex 2 and H and and dose-response curves used to obtain the IC 50 values of the studied compounds on MCF-7 and MRC-5 cells. CCDC Electronic supplementary information (ESI) available: FT-IR spectra of ligand H2Ac4 |
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References_xml | – issn: 2013 publication-title: SHELXS-2013/1: Program for Crystal Structure Solution doi: Sheldrick – issn: 2016 end-page: p 57-67 publication-title: Radiopharmaceuticals for Therapy doi: (Russ) Knapp Dash – issn: 2010 publication-title: Fundamentals of Nuclear Pharmacy doi: Saha – issn: 2014 publication-title: SHELXL-2014/7: Program for the Solution of Crystal Structures doi: Sheldrick – issn: 2009 publication-title: Infrared and Raman Spectra of Inorganic and Coordination Compounds. Part B: Applications in Coordination, Organometallic, and Bioinorganic Chemistry doi: Nakamoto |
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Snippet | In(
iii
) complexes [In(2Ac4
o
ClPh)
2
]NO
3
(
1
) and [In(2Ac4
p
FPh)
2
]NO
3
·1.5H
2
O (
2
) were obtained with
N
(4)-
ortho
-chlorophenyl-2-acetylpyridine... |
SourceID | rsc |
SourceType | Enrichment Source Publisher |
StartPage | 941 |
Title | Neutron activation of In(iii) complexes with thiosemicarbazones leads to the production of potential radiopharmaceuticals for the treatment of breast cancerElectronic supplementary information (ESI) available: FT-IR spectra of ligand H2Ac4oClPh and complex (1), as well as their 1H and 13C{1H} NMR spectra together with the 2D COSY, HMQC and HMBC contour maps used to support the 1H and 13C attributions; X-ray crystallography data and the high resolution mass spectra [ESI(+), IT-TOF] of 1 and 2; an |
Volume | 41 |
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