Mutasim Alfadul, Samah

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  • Mutasim Alfadul, Samah (2)
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Coordination of Ru(II)-Arene Fragments to Dipyridophenazine 2 Ligands Leads to the Modulation of Their In Vitro and In Vivo 3 Anticancer Activity

Nikolić, Stefan; Arakelyan, Jemma; Kushnarev, Vladimir; Mutasim Alfadul, Samah; Stanković, Dalibor; Kraynik, Yaroslav; Grgurić-Šipka, Sanja; Babak, Maria

(Inorganic Chemistry, 2023)

TY  - JOUR
AU  - Nikolić, Stefan
AU  - Arakelyan, Jemma
AU  - Kushnarev, Vladimir
AU  - Mutasim Alfadul, Samah
AU  - Stanković, Dalibor
AU  - Kraynik, Yaroslav
AU  - Grgurić-Šipka, Sanja
AU  - Babak, Maria
PY  - 2023
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5899
AB  - Despite extensive research on the anticancer properties of Ru
complexes with dipyrido[3,2-a:2′,3′-c]phenazine (dppz) ligands, their in vivo
efficacy is rarely investigated. Aiming to understand whether the coordination of
certain half-sandwich Ru(II)-arene fragments might improve the therapeutic
potential of dppz ligands, we prepared a series of Ru(II)-arene complexes with
the general formula [(η6-arene)Ru(dppz-R)Cl]PF6, where the arene fragment
was benzene, toluene, or p-cymene and R was -NO2, -Me, or -COOMe. All
compounds were fully characterized by 1H and 13C NMR spectroscopy and high-
resolution ESI mass-spectrometry, and their purity was verified by elemental
analysis. The electrochemical activity was investigated using cyclic voltammetry.
 The anticancer activity of dppz ligands and their respective Ru complexes was
assessed against several cancer cell lines, and their selectivity toward cancer cells
was assessed using healthy MRC5 lung fibroblasts. The substitution of benzene
with a p-cymene fragment resulted in a more than 17-fold increase of anticancer
activity and selectivity of Ru complexes and significantly enhanced DNA degradation in HCT116 cells. All Ru complexes were electrochemically active in the biologically accessible redox window and were shown to markedly induce the production of ROS in mitochondria. The lead Ru-dppz complex significantly reduced tumor burden in mice with colorectal cancers without inducing liver
 and kidney toxicity.
PB  - Inorganic Chemistry
T2  - Inorganic Chemistry
T1  - Coordination of Ru(II)-Arene Fragments to Dipyridophenazine 2 Ligands Leads to the Modulation of Their In Vitro and In Vivo 3 Anticancer Activity
VL  - 62
SP  - 8188
EP  - 8199
DO  - 10.1021/acs.inorgchem.3c00570
ER  - 
@article{
author = "Nikolić, Stefan and Arakelyan, Jemma and Kushnarev, Vladimir and Mutasim Alfadul, Samah and Stanković, Dalibor and Kraynik, Yaroslav and Grgurić-Šipka, Sanja and Babak, Maria",
year = "2023",
abstract = "Despite extensive research on the anticancer properties of Ru
complexes with dipyrido[3,2-a:2′,3′-c]phenazine (dppz) ligands, their in vivo
efficacy is rarely investigated. Aiming to understand whether the coordination of
certain half-sandwich Ru(II)-arene fragments might improve the therapeutic
potential of dppz ligands, we prepared a series of Ru(II)-arene complexes with
the general formula [(η6-arene)Ru(dppz-R)Cl]PF6, where the arene fragment
was benzene, toluene, or p-cymene and R was -NO2, -Me, or -COOMe. All
compounds were fully characterized by 1H and 13C NMR spectroscopy and high-
resolution ESI mass-spectrometry, and their purity was verified by elemental
analysis. The electrochemical activity was investigated using cyclic voltammetry.
 The anticancer activity of dppz ligands and their respective Ru complexes was
assessed against several cancer cell lines, and their selectivity toward cancer cells
was assessed using healthy MRC5 lung fibroblasts. The substitution of benzene
with a p-cymene fragment resulted in a more than 17-fold increase of anticancer
activity and selectivity of Ru complexes and significantly enhanced DNA degradation in HCT116 cells. All Ru complexes were electrochemically active in the biologically accessible redox window and were shown to markedly induce the production of ROS in mitochondria. The lead Ru-dppz complex significantly reduced tumor burden in mice with colorectal cancers without inducing liver
 and kidney toxicity.",
publisher = "Inorganic Chemistry",
journal = "Inorganic Chemistry",
title = "Coordination of Ru(II)-Arene Fragments to Dipyridophenazine 2 Ligands Leads to the Modulation of Their In Vitro and In Vivo 3 Anticancer Activity",
volume = "62",
pages = "8188-8199",
doi = "10.1021/acs.inorgchem.3c00570"
}
Nikolić, S., Arakelyan, J., Kushnarev, V., Mutasim Alfadul, S., Stanković, D., Kraynik, Y., Grgurić-Šipka, S.,& Babak, M.. (2023). Coordination of Ru(II)-Arene Fragments to Dipyridophenazine 2 Ligands Leads to the Modulation of Their In Vitro and In Vivo 3 Anticancer Activity. in Inorganic Chemistry
Inorganic Chemistry., 62, 8188-8199.
https://doi.org/10.1021/acs.inorgchem.3c00570
Nikolić S, Arakelyan J, Kushnarev V, Mutasim Alfadul S, Stanković D, Kraynik Y, Grgurić-Šipka S, Babak M. Coordination of Ru(II)-Arene Fragments to Dipyridophenazine 2 Ligands Leads to the Modulation of Their In Vitro and In Vivo 3 Anticancer Activity. in Inorganic Chemistry. 2023;62:8188-8199.
doi:10.1021/acs.inorgchem.3c00570 .
Nikolić, Stefan, Arakelyan, Jemma, Kushnarev, Vladimir, Mutasim Alfadul, Samah, Stanković, Dalibor, Kraynik, Yaroslav, Grgurić-Šipka, Sanja, Babak, Maria, "Coordination of Ru(II)-Arene Fragments to Dipyridophenazine 2 Ligands Leads to the Modulation of Their In Vitro and In Vivo 3 Anticancer Activity" in Inorganic Chemistry, 62 (2023):8188-8199,
https://doi.org/10.1021/acs.inorgchem.3c00570 . .
5
3
2

Supplementary material for: Nikolić, S., Arakelyan, J., Kushnarev, V., Mutasim Alfadul, S., Stanković, D., Kraynik, Y., Grgurić-Šipka, S.,& Babak, M.. (2023). Coordination of Ru(II)-Arene Fragments to Dipyridophenazine 2 Ligands Leads to the Modulation of Their In Vitro and In Vivo 3 Anticancer Activity. in Inorganic Chemistry Inorganic Chemistry., 62, 8188-8199. https://doi.org/10.1021/acs.inorgchem.3c00570

Nikolić, Stefan; Arakelyan, Jemma; Kushnarev, Vladimir; Mutasim Alfadul, Samah; Stanković, Dalibor; Kraynik, Yaroslav; Grgurić-Šipka, Sanja; Babak, Maria

(Inorganic Chemistry, 2023)

TY  - DATA
AU  - Nikolić, Stefan
AU  - Arakelyan, Jemma
AU  - Kushnarev, Vladimir
AU  - Mutasim Alfadul, Samah
AU  - Stanković, Dalibor
AU  - Kraynik, Yaroslav
AU  - Grgurić-Šipka, Sanja
AU  - Babak, Maria
PY  - 2023
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5900
AB  - Despite extensive research on the anticancer properties of Rucomplexes with dipyrido[3,2-a:2′,3′-c]phenazine (dppz) ligands, their in vivoefficacy is rarely investigated. Aiming to understand whether the coordination ofcertain half-sandwich Ru(II)-arene fragments might improve the therapeuticpotential of dppz ligands, we prepared a series of Ru(II)-arene complexes withthe general formula [(η6-arene)Ru(dppz-R)Cl]PF6, where the arene fragmentwas benzene, toluene, or p-cymene and R was -NO2, -Me, or -COOMe. Allcompounds were fully characterized by 1H and 13C NMR spectroscopy and high-resolution ESI mass-spectrometry, and their purity was verified by elementalanalysis. The electrochemical activity was investigated using cyclic voltammetry. The anticancer activity of dppz ligands and their respective Ru complexes wasassessed against several cancer cell lines, and their selectivity toward cancer cellswas assessed using healthy MRC5 lung fibroblasts. The substitution of benzenewith a p-cymene fragment resulted in a more than 17-fold increase of anticanceractivity and selectivity of Ru complexes and significantly enhanced DNA degradation in HCT116 cells. All Ru complexes were electrochemically active in the biologically accessible redox window and were shown to markedly induce the production of ROS in mitochondria. The lead Ru-dppz complex significantly reduced tumor burden in mice with colorectal cancers without inducing liver and kidney toxicity.
PB  - Inorganic Chemistry
T2  - Inorganic Chemistry
T1  - Supplementary material for: Nikolić, S., Arakelyan, J., Kushnarev, V., Mutasim Alfadul, S., Stanković, D., Kraynik, Y., Grgurić-Šipka, S.,& Babak, M.. (2023). Coordination of Ru(II)-Arene Fragments to Dipyridophenazine 2 Ligands Leads to the Modulation of Their In Vitro and In Vivo 3 Anticancer Activity. in Inorganic Chemistry Inorganic Chemistry., 62, 8188-8199. https://doi.org/10.1021/acs.inorgchem.3c00570
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5900
ER  - 
@misc{
author = "Nikolić, Stefan and Arakelyan, Jemma and Kushnarev, Vladimir and Mutasim Alfadul, Samah and Stanković, Dalibor and Kraynik, Yaroslav and Grgurić-Šipka, Sanja and Babak, Maria",
year = "2023",
abstract = "Despite extensive research on the anticancer properties of Rucomplexes with dipyrido[3,2-a:2′,3′-c]phenazine (dppz) ligands, their in vivoefficacy is rarely investigated. Aiming to understand whether the coordination ofcertain half-sandwich Ru(II)-arene fragments might improve the therapeuticpotential of dppz ligands, we prepared a series of Ru(II)-arene complexes withthe general formula [(η6-arene)Ru(dppz-R)Cl]PF6, where the arene fragmentwas benzene, toluene, or p-cymene and R was -NO2, -Me, or -COOMe. Allcompounds were fully characterized by 1H and 13C NMR spectroscopy and high-resolution ESI mass-spectrometry, and their purity was verified by elementalanalysis. The electrochemical activity was investigated using cyclic voltammetry. The anticancer activity of dppz ligands and their respective Ru complexes wasassessed against several cancer cell lines, and their selectivity toward cancer cellswas assessed using healthy MRC5 lung fibroblasts. The substitution of benzenewith a p-cymene fragment resulted in a more than 17-fold increase of anticanceractivity and selectivity of Ru complexes and significantly enhanced DNA degradation in HCT116 cells. All Ru complexes were electrochemically active in the biologically accessible redox window and were shown to markedly induce the production of ROS in mitochondria. The lead Ru-dppz complex significantly reduced tumor burden in mice with colorectal cancers without inducing liver and kidney toxicity.",
publisher = "Inorganic Chemistry",
journal = "Inorganic Chemistry",
title = "Supplementary material for: Nikolić, S., Arakelyan, J., Kushnarev, V., Mutasim Alfadul, S., Stanković, D., Kraynik, Y., Grgurić-Šipka, S.,& Babak, M.. (2023). Coordination of Ru(II)-Arene Fragments to Dipyridophenazine 2 Ligands Leads to the Modulation of Their In Vitro and In Vivo 3 Anticancer Activity. in Inorganic Chemistry Inorganic Chemistry., 62, 8188-8199. https://doi.org/10.1021/acs.inorgchem.3c00570",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5900"
}
Nikolić, S., Arakelyan, J., Kushnarev, V., Mutasim Alfadul, S., Stanković, D., Kraynik, Y., Grgurić-Šipka, S.,& Babak, M.. (2023). Supplementary material for: Nikolić, S., Arakelyan, J., Kushnarev, V., Mutasim Alfadul, S., Stanković, D., Kraynik, Y., Grgurić-Šipka, S.,& Babak, M.. (2023). Coordination of Ru(II)-Arene Fragments to Dipyridophenazine 2 Ligands Leads to the Modulation of Their In Vitro and In Vivo 3 Anticancer Activity. in Inorganic Chemistry Inorganic Chemistry., 62, 8188-8199. https://doi.org/10.1021/acs.inorgchem.3c00570. in Inorganic Chemistry
Inorganic Chemistry..
https://hdl.handle.net/21.15107/rcub_cherry_5900
Nikolić S, Arakelyan J, Kushnarev V, Mutasim Alfadul S, Stanković D, Kraynik Y, Grgurić-Šipka S, Babak M. Supplementary material for: Nikolić, S., Arakelyan, J., Kushnarev, V., Mutasim Alfadul, S., Stanković, D., Kraynik, Y., Grgurić-Šipka, S.,& Babak, M.. (2023). Coordination of Ru(II)-Arene Fragments to Dipyridophenazine 2 Ligands Leads to the Modulation of Their In Vitro and In Vivo 3 Anticancer Activity. in Inorganic Chemistry Inorganic Chemistry., 62, 8188-8199. https://doi.org/10.1021/acs.inorgchem.3c00570. in Inorganic Chemistry. 2023;.
https://hdl.handle.net/21.15107/rcub_cherry_5900 .
Nikolić, Stefan, Arakelyan, Jemma, Kushnarev, Vladimir, Mutasim Alfadul, Samah, Stanković, Dalibor, Kraynik, Yaroslav, Grgurić-Šipka, Sanja, Babak, Maria, "Supplementary material for: Nikolić, S., Arakelyan, J., Kushnarev, V., Mutasim Alfadul, S., Stanković, D., Kraynik, Y., Grgurić-Šipka, S.,& Babak, M.. (2023). Coordination of Ru(II)-Arene Fragments to Dipyridophenazine 2 Ligands Leads to the Modulation of Their In Vitro and In Vivo 3 Anticancer Activity. in Inorganic Chemistry Inorganic Chemistry., 62, 8188-8199. https://doi.org/10.1021/acs.inorgchem.3c00570" in Inorganic Chemistry (2023),
https://hdl.handle.net/21.15107/rcub_cherry_5900 .