Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors
Authors
Filipović, Nenad R.Bjelogrlić, Snežana K.

Pelliccia, Sveva

Jovanović, Vesna B.

Kojić, Milan O.

Senćanski, Milan

La Regina, Giuseppe
Silvestri, Romano
Muller, Christian D.
Todorović, Tamara

Article (Published version)
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Triapine, the most studied α-N-heterocyclic thiosemicarbazone, revealed potent activity against advanced leukemia, but was ineffective against a variety of solid tumors. Moreover, methemoglobinemia, which is a side effect of triapine administration, may limits all clinical application. To enhance anticancer activity and reduce side effects, we applied an isosteric replacement of sulfur to selenium atom was performed by synthesis and characterization of selenium triapine analog, 3-aminopyridine-2-carboxaldehyde selenosemicarbazone (selenotriapine). Compared to triapine, selenotriapine revealed superior pro-apoptotic activity with activation of intrinsic apoptotic pathway in both human monocytic leukemia (THP-1) and mammary adenocarcinoma (MCF-7) cell lines. For MCF-7 2-D cultures, selenotriapine induced notable increase in mitochondrial superoxide radical generation and dissipation of mitochondrial transmembrane potential. A significant delay in growth of MCF-7 spheroids (3-D culture) w...as accompanied by phenotypic stem cell reprogramming (Oct-4 expression). Additionally, selenotriapine demonstrated a very low toxicity profile as compared to triapine, confirmed over alleviated extent of methemoglobin formation and higher IC50 value in brine shrimp cytotoxicity assay. © 2017 King Saud University.
Keywords:
3-D culture / Apoptosis / Mitochondrial superoxide production / Oct-4 / SelenosemicarbazoneSource:
Arabian Journal of Chemistry, 2020Funding / projects:
- Interactions of natural products, their derivatives and coordination compounds with proteins and nucleic acids (RS-172055)
- COST Actions CA15135 and CA16119 supported by COST . The work was founded by grants PRIN 2015 no. 2015FCHJ8E (to R.S.)
Note:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3060
DOI: 10.1016/j.arabjc.2017.11.017
ISSN: 1878-5352
WoS: 000505076000109
Scopus: 2-s2.0-85037552505
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Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Filipović, Nenad R. AU - Bjelogrlić, Snežana K. AU - Pelliccia, Sveva AU - Jovanović, Vesna B. AU - Kojić, Milan O. AU - Senćanski, Milan AU - La Regina, Giuseppe AU - Silvestri, Romano AU - Muller, Christian D. AU - Todorović, Tamara PY - 2020 UR - https://cherry.chem.bg.ac.rs/handle/123456789/320 AB - Triapine, the most studied α-N-heterocyclic thiosemicarbazone, revealed potent activity against advanced leukemia, but was ineffective against a variety of solid tumors. Moreover, methemoglobinemia, which is a side effect of triapine administration, may limits all clinical application. To enhance anticancer activity and reduce side effects, we applied an isosteric replacement of sulfur to selenium atom was performed by synthesis and characterization of selenium triapine analog, 3-aminopyridine-2-carboxaldehyde selenosemicarbazone (selenotriapine). Compared to triapine, selenotriapine revealed superior pro-apoptotic activity with activation of intrinsic apoptotic pathway in both human monocytic leukemia (THP-1) and mammary adenocarcinoma (MCF-7) cell lines. For MCF-7 2-D cultures, selenotriapine induced notable increase in mitochondrial superoxide radical generation and dissipation of mitochondrial transmembrane potential. A significant delay in growth of MCF-7 spheroids (3-D culture) was accompanied by phenotypic stem cell reprogramming (Oct-4 expression). Additionally, selenotriapine demonstrated a very low toxicity profile as compared to triapine, confirmed over alleviated extent of methemoglobin formation and higher IC50 value in brine shrimp cytotoxicity assay. © 2017 King Saud University. T2 - Arabian Journal of Chemistry T1 - Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors DO - 10.1016/j.arabjc.2017.11.017 ER -
@article{ author = "Filipović, Nenad R. and Bjelogrlić, Snežana K. and Pelliccia, Sveva and Jovanović, Vesna B. and Kojić, Milan O. and Senćanski, Milan and La Regina, Giuseppe and Silvestri, Romano and Muller, Christian D. and Todorović, Tamara", year = "2020", abstract = "Triapine, the most studied α-N-heterocyclic thiosemicarbazone, revealed potent activity against advanced leukemia, but was ineffective against a variety of solid tumors. Moreover, methemoglobinemia, which is a side effect of triapine administration, may limits all clinical application. To enhance anticancer activity and reduce side effects, we applied an isosteric replacement of sulfur to selenium atom was performed by synthesis and characterization of selenium triapine analog, 3-aminopyridine-2-carboxaldehyde selenosemicarbazone (selenotriapine). Compared to triapine, selenotriapine revealed superior pro-apoptotic activity with activation of intrinsic apoptotic pathway in both human monocytic leukemia (THP-1) and mammary adenocarcinoma (MCF-7) cell lines. For MCF-7 2-D cultures, selenotriapine induced notable increase in mitochondrial superoxide radical generation and dissipation of mitochondrial transmembrane potential. A significant delay in growth of MCF-7 spheroids (3-D culture) was accompanied by phenotypic stem cell reprogramming (Oct-4 expression). Additionally, selenotriapine demonstrated a very low toxicity profile as compared to triapine, confirmed over alleviated extent of methemoglobin formation and higher IC50 value in brine shrimp cytotoxicity assay. © 2017 King Saud University.", journal = "Arabian Journal of Chemistry", title = "Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors", doi = "10.1016/j.arabjc.2017.11.017" }
Filipović, N. R., Bjelogrlić, S. K., Pelliccia, S., Jovanović, V. B., Kojić, M. O., Senćanski, M., La Regina, G., Silvestri, R., Muller, C. D.,& Todorović, T.. (2020). Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors. in Arabian Journal of Chemistry. https://doi.org/10.1016/j.arabjc.2017.11.017
Filipović NR, Bjelogrlić SK, Pelliccia S, Jovanović VB, Kojić MO, Senćanski M, La Regina G, Silvestri R, Muller CD, Todorović T. Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors. in Arabian Journal of Chemistry. 2020;. doi:10.1016/j.arabjc.2017.11.017 .
Filipović, Nenad R., Bjelogrlić, Snežana K., Pelliccia, Sveva, Jovanović, Vesna B., Kojić, Milan O., Senćanski, Milan, La Regina, Giuseppe, Silvestri, Romano, Muller, Christian D., Todorović, Tamara, "Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors" in Arabian Journal of Chemistry (2020), https://doi.org/10.1016/j.arabjc.2017.11.017 . .