New imidoyl-indazole platinum (II) complexes as potential anticancer agents: Synthesis, evaluation of cytotoxicity, cell death and experimental-theoretical DNA interaction studies

Alan R. Cabrera, Christian Espinosa-Bustos, Mario Faúndez, Jaime Meléndez, Pablo Jaque, Constantin G. Daniliuc, Adam Aguirre, Rene S. Rojas, Cristian O. Salas

Resultado de la investigación: Article

6 Citas (Scopus)

Resumen

Four new neutral N,N imidoyl-indazole ligands (L1, L3, L6, L7) and six new Pt(II)-based complexes (C1–5 and C7) were synthesized and characterized by spectroscopic and spectrometric techniques. Additionally, compounds L6, L7, C3, C5 and C7 were analyzed using X-ray diffraction. An evaluation of cytotoxicity and cell death in vitro for both ligands and complexes was performed by colorimetric assay and flow cytometry, in four cancer cell lines and VERO cells as the control, respectively. Cytotoxicity and selectivity demonstrated by each compound were dependent on the cancer cell line assayed. IC50 values of complexes C1–5 and C7 were lower than those exhibited for the reference drug cisplatin, and selectivity of these complexes was in general terms greater than cisplatin on three cancer cell lines studied. In HL60 cells, complexes C1 and C5 exhibited the lowest values of IC50 and were almost five times more selective than cisplatin. Flow cytometry results suggest that each complex predominantly induced necrosis, and its variant necroptosis, instead of apoptosis in all cancer cell lines studied. DNA binding assays, using agarose gel electrophoresis and UV–visible spectrophotometry studies, displayed a strong interaction only between C4 and DNA. In fact, theoretical calculations showed that C4-DNA binding complex was the most thermodynamic favorable interaction among the complexes in study. Overall, induction of cell death by dependent and independent-DNA-metal compound interactions were possible using imidoyl-indazole Pt(II) complexes as anticancer agents.

Idioma originalEnglish
Páginas (desde-hasta)90-101
Número de páginas12
PublicaciónJournal of Inorganic Biochemistry
Volumen174
DOI
EstadoPublished - 1 sep 2017

Huella dactilar

Indazoles
Cell death
Cytotoxicity
Platinum
Antineoplastic Agents
Cell Death
Cells
Cisplatin
Cell Line
Flow cytometry
DNA
Inhibitory Concentration 50
Assays
Neoplasms
Flow Cytometry
Ligands
Agar Gel Electrophoresis
Spectrophotometry
HL-60 Cells
Electrophoresis

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

Citar esto

Cabrera, Alan R. ; Espinosa-Bustos, Christian ; Faúndez, Mario ; Meléndez, Jaime ; Jaque, Pablo ; Daniliuc, Constantin G. ; Aguirre, Adam ; Rojas, Rene S. ; Salas, Cristian O. / New imidoyl-indazole platinum (II) complexes as potential anticancer agents : Synthesis, evaluation of cytotoxicity, cell death and experimental-theoretical DNA interaction studies. En: Journal of Inorganic Biochemistry. 2017 ; Vol. 174. pp. 90-101.
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abstract = "Four new neutral N,N imidoyl-indazole ligands (L1, L3, L6, L7) and six new Pt(II)-based complexes (C1–5 and C7) were synthesized and characterized by spectroscopic and spectrometric techniques. Additionally, compounds L6, L7, C3, C5 and C7 were analyzed using X-ray diffraction. An evaluation of cytotoxicity and cell death in vitro for both ligands and complexes was performed by colorimetric assay and flow cytometry, in four cancer cell lines and VERO cells as the control, respectively. Cytotoxicity and selectivity demonstrated by each compound were dependent on the cancer cell line assayed. IC50 values of complexes C1–5 and C7 were lower than those exhibited for the reference drug cisplatin, and selectivity of these complexes was in general terms greater than cisplatin on three cancer cell lines studied. In HL60 cells, complexes C1 and C5 exhibited the lowest values of IC50 and were almost five times more selective than cisplatin. Flow cytometry results suggest that each complex predominantly induced necrosis, and its variant necroptosis, instead of apoptosis in all cancer cell lines studied. DNA binding assays, using agarose gel electrophoresis and UV–visible spectrophotometry studies, displayed a strong interaction only between C4 and DNA. In fact, theoretical calculations showed that C4-DNA binding complex was the most thermodynamic favorable interaction among the complexes in study. Overall, induction of cell death by dependent and independent-DNA-metal compound interactions were possible using imidoyl-indazole Pt(II) complexes as anticancer agents.",
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New imidoyl-indazole platinum (II) complexes as potential anticancer agents : Synthesis, evaluation of cytotoxicity, cell death and experimental-theoretical DNA interaction studies. / Cabrera, Alan R.; Espinosa-Bustos, Christian; Faúndez, Mario; Meléndez, Jaime; Jaque, Pablo; Daniliuc, Constantin G.; Aguirre, Adam; Rojas, Rene S.; Salas, Cristian O.

En: Journal of Inorganic Biochemistry, Vol. 174, 01.09.2017, p. 90-101.

Resultado de la investigación: Article

TY - JOUR

T1 - New imidoyl-indazole platinum (II) complexes as potential anticancer agents

T2 - Synthesis, evaluation of cytotoxicity, cell death and experimental-theoretical DNA interaction studies

AU - Cabrera, Alan R.

AU - Espinosa-Bustos, Christian

AU - Faúndez, Mario

AU - Meléndez, Jaime

AU - Jaque, Pablo

AU - Daniliuc, Constantin G.

AU - Aguirre, Adam

AU - Rojas, Rene S.

AU - Salas, Cristian O.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Four new neutral N,N imidoyl-indazole ligands (L1, L3, L6, L7) and six new Pt(II)-based complexes (C1–5 and C7) were synthesized and characterized by spectroscopic and spectrometric techniques. Additionally, compounds L6, L7, C3, C5 and C7 were analyzed using X-ray diffraction. An evaluation of cytotoxicity and cell death in vitro for both ligands and complexes was performed by colorimetric assay and flow cytometry, in four cancer cell lines and VERO cells as the control, respectively. Cytotoxicity and selectivity demonstrated by each compound were dependent on the cancer cell line assayed. IC50 values of complexes C1–5 and C7 were lower than those exhibited for the reference drug cisplatin, and selectivity of these complexes was in general terms greater than cisplatin on three cancer cell lines studied. In HL60 cells, complexes C1 and C5 exhibited the lowest values of IC50 and were almost five times more selective than cisplatin. Flow cytometry results suggest that each complex predominantly induced necrosis, and its variant necroptosis, instead of apoptosis in all cancer cell lines studied. DNA binding assays, using agarose gel electrophoresis and UV–visible spectrophotometry studies, displayed a strong interaction only between C4 and DNA. In fact, theoretical calculations showed that C4-DNA binding complex was the most thermodynamic favorable interaction among the complexes in study. Overall, induction of cell death by dependent and independent-DNA-metal compound interactions were possible using imidoyl-indazole Pt(II) complexes as anticancer agents.

AB - Four new neutral N,N imidoyl-indazole ligands (L1, L3, L6, L7) and six new Pt(II)-based complexes (C1–5 and C7) were synthesized and characterized by spectroscopic and spectrometric techniques. Additionally, compounds L6, L7, C3, C5 and C7 were analyzed using X-ray diffraction. An evaluation of cytotoxicity and cell death in vitro for both ligands and complexes was performed by colorimetric assay and flow cytometry, in four cancer cell lines and VERO cells as the control, respectively. Cytotoxicity and selectivity demonstrated by each compound were dependent on the cancer cell line assayed. IC50 values of complexes C1–5 and C7 were lower than those exhibited for the reference drug cisplatin, and selectivity of these complexes was in general terms greater than cisplatin on three cancer cell lines studied. In HL60 cells, complexes C1 and C5 exhibited the lowest values of IC50 and were almost five times more selective than cisplatin. Flow cytometry results suggest that each complex predominantly induced necrosis, and its variant necroptosis, instead of apoptosis in all cancer cell lines studied. DNA binding assays, using agarose gel electrophoresis and UV–visible spectrophotometry studies, displayed a strong interaction only between C4 and DNA. In fact, theoretical calculations showed that C4-DNA binding complex was the most thermodynamic favorable interaction among the complexes in study. Overall, induction of cell death by dependent and independent-DNA-metal compound interactions were possible using imidoyl-indazole Pt(II) complexes as anticancer agents.

KW - Cell death

KW - Cytotoxicity

KW - DNA binding

KW - Imidoyl-indazoles

KW - Platinum (II)

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U2 - 10.1016/j.jinorgbio.2017.06.001

DO - 10.1016/j.jinorgbio.2017.06.001

M3 - Article

AN - SCOPUS:85021067041

VL - 174

SP - 90

EP - 101

JO - Journal of Inorganic Biochemistry

JF - Journal of Inorganic Biochemistry

SN - 0162-0134

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