Synthesis, characterization, biomolecular interactions, molecular docking, and in vitro and in vivo anticancer activities of novel ruthenium(III) Schiff base complexes
Објеката
- Тип
- Рад у часопису
- Верзија рада
- објављена верзија
- Језик
- енглески
- Креатор
- Milica Međedović, Aleksandar Mijatović, Rada Baošić, Dejan Lazić, Žiko Milanović, Zoran Marković, Jelena Milovanović, Dragana Arsenijević, Bojana Stojanović, Miloš Arsenijević, Marija Milovanović, Biljana Petrović, Ana Rilak Simović
- Извор
- Journal of Inorganic Biochemistry
- Издавач
- Elsevier BV
- Датум издавања
- 2023
- Сажетак
- In order to discover new anticancer drugs, novel ruthenium(III) complexes [Ru(L)Cl(H2O)], where L is tetradentate Schiff base bis(acetylacetone)ethylendiimine (acacen, 1), bis(benzoylacetone)ethylendiimine (bzacen, 2), (acetylacetone)(benzoylaceton)ethylendiimine (acacbzacen, 3), bis(acetylacetone)propylendiimine (acacpn, 4), bis(benzoylacetone)propylendiimine (bzacpn, 5) or (acetylacetone)(benzoylaceton)propylendiimine (acacbzacpn, 6), were synthesized. The complexes 1 – 6 were characterized by elemental analysis, molar conductometry, and by various spectroscopic techniques, such as UV–Vis, IR, EPR, and ESI-MS. Based on in vitro DNA/BSA experiments, complexes 2 (bzacen) and 5 (bzacpn) with two aromatic rings showed the highest DNA/ BSA-activity, suggesting that the presence of the aromatic ring on the tetradentate Schiff base ligand contributes to increased activity. Moreover, these two compounds showed the highest cytotoxic effects toward human, A549 and murine LLC1 lung cancer cells. These complexes altered the ratio of anti- and pro-apoptotic molecules and induced apoptosis of A549 cells. Further, complexes 2 and 5 reduced the percentage of Mcl1 and Bcl2 expressing LLC1 cells, induced their apoptotic death and exerted an antiproliferative effect against LLC1. Finally, complex 5 reduced the volume of mouse primary heterotopic Lewis lung cancer, while complex 2 reduced the incidence and mean number of metastases per lung. Additionally, molecular docking with DNA revealed that the reduced number of aromatic rings or their absence causes lower intercalative properties of the complexes in order: 2 > 5 > 6 > 3 > 4 > 1. It was observed that conventional hydrogen bonds and hydrophobic interactions contribute to the stabilization of the structures of complex-DNA. A molecular docking study with BSA revealed a predominance of 1 – 6 in binding affinity to the active site III, a third D-shaped hydrophobic pocket within subdomain IB.
- том
- 248
- Број
- -
- почетак странице
- 112363
- doi
- 10.1016/j.jinorgbio.2023.112363
- issn
- 0162-0134
- Subject
- Inorganic Chemistry, Biochemistry
- Шира категорија рада
- M20
- Ужа категорија рада
- М21
- Права
- Затворени приступ
- Лиценца
- Creative Commons – Attribution-No Derivative Works 4.0 International
- Формат
Milica Međedović, Aleksandar Mijatović, Rada Baošić, Dejan Lazić, Žiko Milanović, Zoran Marković, Jelena Milovanović, Dragana Arsenijević, Bojana Stojanović, Miloš Arsenijević, Marija Milovanović, Biljana Petrović, Ana Rilak Simović. "Synthesis, characterization, biomolecular interactions, molecular docking, and in vitro and in vivo anticancer activities of novel ruthenium(III) Schiff base complexes" in Journal of Inorganic Biochemistry, Elsevier BV (2023). https://doi.org/10.1016/j.jinorgbio.2023.112363
This item was submitted on 13. октобар 2023. by [anonymous user] using the form “Рад у часопису” on the site “Радови”: http://drug.rgf.bg.ac.rs/s/repo
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