A new class of platinum(II) complexes with the phosphine ligand pta which show potent anticancer activity

2018
Authors
Živković, Marija
Kljun, Jakob
Ilić-Tomić, Tatjana

Pavić, Aleksandar

Veselinovic, A.
Manojlović, Dragan D.

Nikodinović-Runić, Jasmina

Turel, Iztok

Article (Published version)
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Show full item recordAbstract
The anticancer potential of sixteen platinum(II) complexes with general formulae [PtCl(hq)(S-dmso)] (1a-8a) and [PtCl(hq)(pta)] (1b-8b) (where hq is 5-chloro-7-iodo-8-quinolinol (clioquinol; cqH) (1a, 1b), 8-hydroxy-5-nitroquinoline (nitroxoline; nxH) (2a, 2b), 5,7-dichloro-8-quinolinol (3a, 3b), 5,7-diiodo-8-quinolinol (4a, 4b), 5,7-dibromo-8-quinolinol (5a, 5b), 5,7-dichloro-8-hydroxy-2-methyl-quinoline (6a, 6b), 8-hydroxyquinoline (7a, 7b) and 8-quinolinethiol (8a, 8b); dmso is dimethyl sulfoxide and pta is 1,3,5triaza- 7-phosphaadamantane) was determined through in vitro cytotoxicity assay in human fibroblasts (MRC5) and two carcinoma cell lines (A375 and A549) and embryotoxicity assay in a zebrafish model. Interactions with double stranded DNA through in vitro assay and a molecular docking study were examined. All complexes, except 6a, exhibited a high cytotoxic effect on MRC5 cells at a concentration of 10 mu g mL(-1) while 1b, 5a, 6a and 3b showed selective toxicity towards carc...inoma cell lines. In general, pta-based complexes (series b) were more toxic according to the results of a MTT screen and the LC50 values obtained in zebrafish (Danio rerio) assay; they also induced higher oxidative stress in this model. Successful cellular uptake of complexes was shown by the ICP-MS methodology. The binding propensity of the complex with DNA obtained in in silico studies can be correlated with those from the experimental investigation. Compounds with the highest binding potential, according to the interaction energy value, were 1b, 3b, 6b and 5b. From observations of the DNA interaction ability and of the in silico assessment, no apparent DNA fragmentation was observed either on DNA extracted from the treated cancer cell line or from the zebrafish embryos.
Source:
INORGANIC CHEMISTRY FRONTIERS, 2018, 5, 1, 39-53Publisher:
- Royal Soc Chemistry, Cambridge
Funding / projects:
- Synthesis of new metal complexes and investigation of their reactions with peptides (RS-172036)
- Microbial diversity study and characterization of beneficial environmental microorganisms (RS-173048)
- bilateral Slovenian-Serbian project [BI-RS/16-17-024]
- Slovenian Research Agency [P1-0175, Z1-6735]
- Erasmus Mundus Action 2 Project Basileus V
Note:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3144
DOI: 10.1039/c7qi00299h
ISSN: 2052-1553
WoS: 000422862800003
Scopus: 2-s2.0-85040815907
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Institution/Community
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Živković, Marija AU - Kljun, Jakob AU - Ilić-Tomić, Tatjana AU - Pavić, Aleksandar AU - Veselinovic, A. AU - Manojlović, Dragan D. AU - Nikodinović-Runić, Jasmina AU - Turel, Iztok PY - 2018 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2071 AB - The anticancer potential of sixteen platinum(II) complexes with general formulae [PtCl(hq)(S-dmso)] (1a-8a) and [PtCl(hq)(pta)] (1b-8b) (where hq is 5-chloro-7-iodo-8-quinolinol (clioquinol; cqH) (1a, 1b), 8-hydroxy-5-nitroquinoline (nitroxoline; nxH) (2a, 2b), 5,7-dichloro-8-quinolinol (3a, 3b), 5,7-diiodo-8-quinolinol (4a, 4b), 5,7-dibromo-8-quinolinol (5a, 5b), 5,7-dichloro-8-hydroxy-2-methyl-quinoline (6a, 6b), 8-hydroxyquinoline (7a, 7b) and 8-quinolinethiol (8a, 8b); dmso is dimethyl sulfoxide and pta is 1,3,5triaza- 7-phosphaadamantane) was determined through in vitro cytotoxicity assay in human fibroblasts (MRC5) and two carcinoma cell lines (A375 and A549) and embryotoxicity assay in a zebrafish model. Interactions with double stranded DNA through in vitro assay and a molecular docking study were examined. All complexes, except 6a, exhibited a high cytotoxic effect on MRC5 cells at a concentration of 10 mu g mL(-1) while 1b, 5a, 6a and 3b showed selective toxicity towards carcinoma cell lines. In general, pta-based complexes (series b) were more toxic according to the results of a MTT screen and the LC50 values obtained in zebrafish (Danio rerio) assay; they also induced higher oxidative stress in this model. Successful cellular uptake of complexes was shown by the ICP-MS methodology. The binding propensity of the complex with DNA obtained in in silico studies can be correlated with those from the experimental investigation. Compounds with the highest binding potential, according to the interaction energy value, were 1b, 3b, 6b and 5b. From observations of the DNA interaction ability and of the in silico assessment, no apparent DNA fragmentation was observed either on DNA extracted from the treated cancer cell line or from the zebrafish embryos. PB - Royal Soc Chemistry, Cambridge T2 - INORGANIC CHEMISTRY FRONTIERS T1 - A new class of platinum(II) complexes with the phosphine ligand pta which show potent anticancer activity VL - 5 IS - 1 SP - 39 EP - 53 DO - 10.1039/c7qi00299h ER -
@article{ author = "Živković, Marija and Kljun, Jakob and Ilić-Tomić, Tatjana and Pavić, Aleksandar and Veselinovic, A. and Manojlović, Dragan D. and Nikodinović-Runić, Jasmina and Turel, Iztok", year = "2018", abstract = "The anticancer potential of sixteen platinum(II) complexes with general formulae [PtCl(hq)(S-dmso)] (1a-8a) and [PtCl(hq)(pta)] (1b-8b) (where hq is 5-chloro-7-iodo-8-quinolinol (clioquinol; cqH) (1a, 1b), 8-hydroxy-5-nitroquinoline (nitroxoline; nxH) (2a, 2b), 5,7-dichloro-8-quinolinol (3a, 3b), 5,7-diiodo-8-quinolinol (4a, 4b), 5,7-dibromo-8-quinolinol (5a, 5b), 5,7-dichloro-8-hydroxy-2-methyl-quinoline (6a, 6b), 8-hydroxyquinoline (7a, 7b) and 8-quinolinethiol (8a, 8b); dmso is dimethyl sulfoxide and pta is 1,3,5triaza- 7-phosphaadamantane) was determined through in vitro cytotoxicity assay in human fibroblasts (MRC5) and two carcinoma cell lines (A375 and A549) and embryotoxicity assay in a zebrafish model. Interactions with double stranded DNA through in vitro assay and a molecular docking study were examined. All complexes, except 6a, exhibited a high cytotoxic effect on MRC5 cells at a concentration of 10 mu g mL(-1) while 1b, 5a, 6a and 3b showed selective toxicity towards carcinoma cell lines. In general, pta-based complexes (series b) were more toxic according to the results of a MTT screen and the LC50 values obtained in zebrafish (Danio rerio) assay; they also induced higher oxidative stress in this model. Successful cellular uptake of complexes was shown by the ICP-MS methodology. The binding propensity of the complex with DNA obtained in in silico studies can be correlated with those from the experimental investigation. Compounds with the highest binding potential, according to the interaction energy value, were 1b, 3b, 6b and 5b. From observations of the DNA interaction ability and of the in silico assessment, no apparent DNA fragmentation was observed either on DNA extracted from the treated cancer cell line or from the zebrafish embryos.", publisher = "Royal Soc Chemistry, Cambridge", journal = "INORGANIC CHEMISTRY FRONTIERS", title = "A new class of platinum(II) complexes with the phosphine ligand pta which show potent anticancer activity", volume = "5", number = "1", pages = "39-53", doi = "10.1039/c7qi00299h" }
Živković, M., Kljun, J., Ilić-Tomić, T., Pavić, A., Veselinovic, A., Manojlović, D. D., Nikodinović-Runić, J.,& Turel, I.. (2018). A new class of platinum(II) complexes with the phosphine ligand pta which show potent anticancer activity. in INORGANIC CHEMISTRY FRONTIERS Royal Soc Chemistry, Cambridge., 5(1), 39-53. https://doi.org/10.1039/c7qi00299h
Živković M, Kljun J, Ilić-Tomić T, Pavić A, Veselinovic A, Manojlović DD, Nikodinović-Runić J, Turel I. A new class of platinum(II) complexes with the phosphine ligand pta which show potent anticancer activity. in INORGANIC CHEMISTRY FRONTIERS. 2018;5(1):39-53. doi:10.1039/c7qi00299h .
Živković, Marija, Kljun, Jakob, Ilić-Tomić, Tatjana, Pavić, Aleksandar, Veselinovic, A., Manojlović, Dragan D., Nikodinović-Runić, Jasmina, Turel, Iztok, "A new class of platinum(II) complexes with the phosphine ligand pta which show potent anticancer activity" in INORGANIC CHEMISTRY FRONTIERS, 5, no. 1 (2018):39-53, https://doi.org/10.1039/c7qi00299h . .