Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification
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2019
Authors
Bjelogrlić, Snežana K.Todorović, Tamara
Kojić, Milan O.
Senćanski, Milan V.
Nikolić, Milan R.
Višnjevac, Aleksandar
Araškov, Jovana
Miljković, Marija S.
Muller, Christian D.
Filipović, Nenad R.
Article (Published version)
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© 2019 Elsevier Inc
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Anticancer activity of Pd complexes 1–5 with bidentate N-heteroaromatic hydrazone ligands was investigated on human acute monocytic leukemia (THP-1; cells in a suspension) and human mammary adenocarcinoma (MCF-7; two-dimensional layer and three-dimensional spheroid tumor model) cell lines. For the Pd(II) complexes with condensation products of ethyl hydrazainoacetate and quinoline-8-carboxaldehyde (complex 1) and 2-formylpyridine (complex 3), for which apoptosis was determined as a mechanism of anticancer activity, further investigation revealed that they arrest the cell cycle in G0/G1 phase, induce generation of reactive oxygen species and inhibit Topoisomerase I in vitro. In silico studies corroborate experimental findings that these complexes show topoisomerase inhibition activity in the micromolar range and indicate binding to a DNA's minor groove as another potential target. Based on the results obtained by circular dichroism and fluorescence spectroscopy measurements, the most ac...tive complexes are suitable to be delivered to a blood stream via human serum albumin.
Keywords:
Apoptosis / DNA interactions / HSA interactions / Hydrazones / Pd(II) complexes / Topoisomerase I inhibitionSource:
Journal of Inorganic Biochemistry, 2019, 199, UNSP 110758-Funding / projects:
- Interactions of natural products, their derivatives and coordination compounds with proteins and nucleic acids (RS-MESTD-Basic Research (BR or ON)-172055)
- COST Actions [CA15135]
- COST Actions [CA16119]
Note:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3319
DOI: 10.1016/j.jinorgbio.2019.110758
ISSN: 0162-0134; 1873-3344
PubMed: 31299379
WoS: 000488146900009
Scopus: 2-s2.0-85068530825
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VinčaTY - JOUR AU - Bjelogrlić, Snežana K. AU - Todorović, Tamara AU - Kojić, Milan O. AU - Senćanski, Milan V. AU - Nikolić, Milan R. AU - Višnjevac, Aleksandar AU - Araškov, Jovana AU - Miljković, Marija S. AU - Muller, Christian D. AU - Filipović, Nenad R. PY - 2019 UR - https://vinar.vin.bg.ac.rs/handle/123456789/8382 AB - Anticancer activity of Pd complexes 1–5 with bidentate N-heteroaromatic hydrazone ligands was investigated on human acute monocytic leukemia (THP-1; cells in a suspension) and human mammary adenocarcinoma (MCF-7; two-dimensional layer and three-dimensional spheroid tumor model) cell lines. For the Pd(II) complexes with condensation products of ethyl hydrazainoacetate and quinoline-8-carboxaldehyde (complex 1) and 2-formylpyridine (complex 3), for which apoptosis was determined as a mechanism of anticancer activity, further investigation revealed that they arrest the cell cycle in G0/G1 phase, induce generation of reactive oxygen species and inhibit Topoisomerase I in vitro. In silico studies corroborate experimental findings that these complexes show topoisomerase inhibition activity in the micromolar range and indicate binding to a DNA's minor groove as another potential target. Based on the results obtained by circular dichroism and fluorescence spectroscopy measurements, the most active complexes are suitable to be delivered to a blood stream via human serum albumin. T2 - Journal of Inorganic Biochemistry T1 - Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification VL - 199 SP - UNSP 110758 DO - 10.1016/j.jinorgbio.2019.110758 ER -
@article{ author = "Bjelogrlić, Snežana K. and Todorović, Tamara and Kojić, Milan O. and Senćanski, Milan V. and Nikolić, Milan R. and Višnjevac, Aleksandar and Araškov, Jovana and Miljković, Marija S. and Muller, Christian D. and Filipović, Nenad R.", year = "2019", abstract = "Anticancer activity of Pd complexes 1–5 with bidentate N-heteroaromatic hydrazone ligands was investigated on human acute monocytic leukemia (THP-1; cells in a suspension) and human mammary adenocarcinoma (MCF-7; two-dimensional layer and three-dimensional spheroid tumor model) cell lines. For the Pd(II) complexes with condensation products of ethyl hydrazainoacetate and quinoline-8-carboxaldehyde (complex 1) and 2-formylpyridine (complex 3), for which apoptosis was determined as a mechanism of anticancer activity, further investigation revealed that they arrest the cell cycle in G0/G1 phase, induce generation of reactive oxygen species and inhibit Topoisomerase I in vitro. In silico studies corroborate experimental findings that these complexes show topoisomerase inhibition activity in the micromolar range and indicate binding to a DNA's minor groove as another potential target. Based on the results obtained by circular dichroism and fluorescence spectroscopy measurements, the most active complexes are suitable to be delivered to a blood stream via human serum albumin.", journal = "Journal of Inorganic Biochemistry", title = "Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification", volume = "199", pages = "UNSP 110758", doi = "10.1016/j.jinorgbio.2019.110758" }
Bjelogrlić, S. K., Todorović, T., Kojić, M. O., Senćanski, M. V., Nikolić, M. R., Višnjevac, A., Araškov, J., Miljković, M. S., Muller, C. D.,& Filipović, N. R.. (2019). Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification. in Journal of Inorganic Biochemistry, 199, UNSP 110758. https://doi.org/10.1016/j.jinorgbio.2019.110758
Bjelogrlić SK, Todorović T, Kojić MO, Senćanski MV, Nikolić MR, Višnjevac A, Araškov J, Miljković MS, Muller CD, Filipović NR. Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification. in Journal of Inorganic Biochemistry. 2019;199:UNSP 110758. doi:10.1016/j.jinorgbio.2019.110758 .
Bjelogrlić, Snežana K., Todorović, Tamara, Kojić, Milan O., Senćanski, Milan V., Nikolić, Milan R., Višnjevac, Aleksandar, Araškov, Jovana, Miljković, Marija S., Muller, Christian D., Filipović, Nenad R., "Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification" in Journal of Inorganic Biochemistry, 199 (2019):UNSP 110758, https://doi.org/10.1016/j.jinorgbio.2019.110758 . .