Journal of Inorganic Biochemistry最新文献

{"title":"A series of DNA targeted Cu (II) complexes containing 1,8-naphthalimide ligands: Synthesis, characterization and in vitro anticancer activity","authors":"","doi":"10.1016/j.jinorgbio.2024.112721","DOIUrl":"10.1016/j.jinorgbio.2024.112721","url":null,"abstract":"<div><p>Copper(II) complexes are very promising candidates for platinum-based anticancer agents. Herein, three Cu (II) complexes (<strong>1</strong>–<strong>3</strong>) containing 1,8-naphthalimide ligands were synthesized and characterized by FT-IR, elemental analysis, ESI-MS and single crystal X-ray diffraction (complex <strong>3</strong>). In addition, a control compound (complex <strong>4</strong>) without 1,8-naphthalimide ligand was synthesized and characterized. The in vitro anticancer activity of the synthesized complexes against five cancer cell lines and one normal cell line was evaluated by MTS assay. The results displayed the antitumor activity of complexes <strong>1</strong>–<strong>3</strong> was controlled by the aliphatic chain length of ligands, their cytotoxicity was in the order <strong>3</strong> &gt; <strong>2</strong> &gt; <strong>1</strong>, giving the IC₅₀ values ranging from 2.874 ± 0.155 μM to 31.47 ± 0.29 μM against five cancer cell lines. Complex <strong>4</strong> showed less activity in comparison with complex <strong>1</strong>–<strong>3</strong>. Notably, complexes <strong>1</strong>–<strong>3</strong> displayed much higher selectivity (SI = 2.65 to 10.16) compared to complex <strong>4</strong> (SI = 1.0), indicated that the introduction of 1,8-naphthalimide group not only increased the activity of this series of compounds but also enhanced their specific selectivity to cancer cells. Compound <strong>3</strong> induced apoptosis in cancer cells and blocked the S-phase and G2/M of cancer cells. The interaction with DNA of complexes <strong>3</strong> and <strong>4</strong> was studied by UV/Vis spectroscopic titrations, competitive DNA-binding experiment, viscometry and CD spectra. The results showed that complex <strong>3</strong> interacted with DNA in an intercalating mode, but the interaction mode of compound <strong>4</strong> with DNA was electrostatic interaction.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142128264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, characterization, and biological activities of novel Ag(I)-NHC complexes based on 1,3-dioxane ligand","authors":"","doi":"10.1016/j.jinorgbio.2024.112719","DOIUrl":"10.1016/j.jinorgbio.2024.112719","url":null,"abstract":"<div><p>Herein, a series of new Ag(I)-NHC complexes containing 1,3-dioxane group were synthesized by the direct reaction of Ag₂O and benzimidazolium salts in light-free conditions. All Ag(I)-NHC complexes were spectrally characterized using ¹H, ¹³C NMR, FT-IR, LC-MS, and elemental analysis. Additionally, the structures of compounds <strong>1a</strong> and <strong>1e</strong> were elucidated by the single X-ray diffraction techniques. Further, the synthesized Ag(I)-NHC complexes were evaluated for cytotoxicity study on the L-929 cells and the anticancer activity against the HCT 116 and MCF-7 cancer cell lines. Notably, <strong>1a</strong> showed significant anticancer activity against HCT 116 with an IC₅₀ of 6.37 ± 0.92 μg/mL compared to cisplatin (IC₅₀ = 36.75 ± 1.76 μg/mL). <strong>1c</strong> (IC₅₀ = 3.21 ± 1.96 μg/mL) and <strong>1e</strong> (IC₅₀ = 3.72 ± 1.12 μg/mL) exhibited significant anticancer activity against MCF-7 cells and was similar to cisplatin (IC₅₀ = 32.17 ± 2.85 μg/mL). Meanwhile, <strong>1a</strong> and <strong>1e</strong> displayed the highest selectivity index. Most importantly, the cell viability test showed that <strong>1e</strong> induced neglectable cytotoxicity (IC₅₀ = 36.38 ± 2.27 μg/mL) toward L-929 and was similar to cisplatin (IC₅₀ = 36.11 ± 2.09 μg/mL). The anticancer activities of Ag(I)-NHC complexes vary depending on the substituent group of the silver complex and the cell line type. Moreover, the inhibitory mechanism of <strong>1e</strong> was not dependent on caspase-associated apoptosis initiated by the lysosomal-mitochondrial pathway. Taken together, we conclude that this work provides a simple and rapid protocol for the synthesis of Ag(I)-NHC complexes and the featured Ag(I)-NHC complexes have an anticancer drug potential for biomedical applications.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A structural and functional model for alkene dioxygenases","authors":"","doi":"10.1016/j.jinorgbio.2024.112718","DOIUrl":"10.1016/j.jinorgbio.2024.112718","url":null,"abstract":"<div><p>In this article, we report sterically-controlled iron sites based on non-chelating bulky imidazole ligands. Adding 6 equiv. of 1,2-dimethylimidazole (1,2-Me₂Im) to Fe(OTf)₂⋅2CH₃CN affords the first example of a 5-coordinate imidazole‑iron complex ([Fe(1,2-Me₂Im)₅](OTf)₂, <strong>1</strong>). The structure is distorted square pyramidal (τ₅ = 0.41). When an ^<em>i</em>Pr group is substituted for the methyl group at the 2-position on the imidazole (2-^<em>i</em>Pr-1-MeIm), the 14-electron complex ([Fe(2-^<em>i</em>Pr-1-MeIm)₄](OTf)₂, <strong>2</strong>) is obtained. This complex exhibits slightly distorted tetrahedral geometry (τ'₄ = 0.93) with four N-donors and serves as a 4-His iron structural model complex for carotenoid cleavage dioxygenases (CCD). The electronic structure of <strong>1</strong> and <strong>2</strong> were characterized by Mössbauer spectroscopy. Reactions of <strong>1</strong> and <strong>2</strong> with model olefin substrates (1-R-4-(1-methoxyprop-1-en-2-yl)benzene; R = Me or Br) in the presence of oxygen result in olefin cleavage yielding ketone and aldehyde products, although <strong>2</strong> yields more products than <strong>1</strong>. Support for a proposed reaction mechanism for <strong>2</strong> is offered from Density Functional Theory (DFT) calculations.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heme-based dioxygenases: Structure, function and dynamics","authors":"","doi":"10.1016/j.jinorgbio.2024.112707","DOIUrl":"10.1016/j.jinorgbio.2024.112707","url":null,"abstract":"<div><p>Tryptophan dioxygenase (TDO) and indoleamine 2,3 dioxygenase (IDO) belong to a unique class of heme-based enzymes that insert dioxygen into the essential amino acid, L-tryptophan (Trp), to generate N-formylkynurenine (NFK), a critical metabolite in the kynurenine pathway. Recently, the two dioxygenases were recognized as pivotal cancer immunotherapeutic drug targets, which triggered a great deal of drug discovery targeting them. The advancement of the field is however hampered by the poor understanding of the structural properties of the two enzymes and the mechanisms by which the structures dictate their functions. In this review, we summarize recent findings centered on the structure, function, and dynamics of the human isoforms of the two enzymes.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Significant enhancement of anticancer effect of iridium (III) complexes encapsulated in liposomes","authors":"","doi":"10.1016/j.jinorgbio.2024.112706","DOIUrl":"10.1016/j.jinorgbio.2024.112706","url":null,"abstract":"<div><p>In this study, the ligand EIPP (5-ethoxy-2-(1H-imidazo[4,5-f] [<span><span>1</span></span>,<span><span>10</span></span>] phenanthrolin-2-yl)phenol) and [Ir(ppy)₂(EIPP)](PF₆)] (5a, ppy = 2-phenylpyridine) and [Ir(piq)₂(EIPP)](PF₆)] (5b, piq = 1-phenylisoquinoline) were synthesized and they were entrapped into liposomes to produce 5alipo and 5blipo. 5a and 5b were characterized via HRMS, NMR, UV–vis and IR. The cytotoxicity of 5a, 5b, 5alipo and 5blipo on cancer and non-cancer cells was estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). MTT assay demonstrated that 5a and 5b did not show any significant cellular activity but their liposome-encapsulated 5alipo and 5blipo had significant toxic effects. The mechanism of 5alipo, 5blipo-inducing apoptosis was explored by studying cellular uptake, mitochondrial localization, mitochondrial membrane potential, cytochrome C, glutathione (GSH), malondialdehyde (MDA) and protein immunoblotting. The results demonstrated that 5alipo and 5blipo caused a release of cytochrome C, downregulated the expression of Bcl-2, upregulated the expression of BAX, activated caspase 3, and downregulated PARP expression. It was shown that 5alipo and 5blipo could inhibit cancer cell proliferation in G2/M phase by regulating p53 and p21 proteins. Additionally, 5alipo and 5blipo induced autophagy through an adjustment from LC3-I to LC3-II and caused ferroptosis. The in vivo antitumor activity of 5alipo was examined in detail</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142086792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A refreshing approach to understanding the action on DNA of vanadium (IV) and (V) complexes derived from the anticancer VCp2Cl2","authors":"","doi":"10.1016/j.jinorgbio.2024.112705","DOIUrl":"10.1016/j.jinorgbio.2024.112705","url":null,"abstract":"<div><p>A computational study based on derivatives of the anticancer <span><math><msub><mi>VCp</mi><mn>2</mn></msub><msub><mi>Cl</mi><mn>2</mn></msub></math></span> compound and their interaction with representative models of deoxyribonucleic acid (DNA) is presented. The derivatives were obtained by substituting the cyclopentadienes of <span><math><msub><mi>VCp</mi><mn>2</mn></msub><msub><mi>Cl</mi><mn>2</mn></msub></math></span> with <span><math><msub><mi>H</mi><mn>2</mn></msub><mi>O</mi></math></span>, <span><math><msub><mi>NH</mi><mn>3</mn></msub></math></span>, <span><math><msup><mi>OH</mi><mo>−</mo></msup></math></span>, <span><math><msup><mi>Cl</mi><mo>−</mo></msup></math></span>, <span><math><msup><mi>O</mi><mrow><mn>2</mn><mo>−</mo></mrow></msup></math></span> and <span><math><msub><mi>C</mi><mn>2</mn></msub><msubsup><mi>O</mi><mn>4</mn><mrow><mn>2</mn><mo>−</mo></mrow></msubsup></math></span> ligands. The oxidation states IV and V of vanadium were considered, so a total of 20 derivative complexes are included. The complexes interactions with DNA were studied using two different models, the first model considers the interactions of the complexes with the pair Guanine-Cytosine (G-C) and the second involves the interaction of the complexes with adjacent pairs, that is, d(GG). This study compares methodologies based on density functional theory with coupled cluster like calculations (DLPNO-CCSD(T)), the gold standard of electronic structure methods. Furthermore, the change in the electron density of the hydrogen bonds that keep bonded the G-C pair and d(GG) pairs, due to the presence of vanadium (IV) and (V) complexes is rationalize. To this aim, quantities obtained from the topology of the electron densities are inspected, particularly the value of the electron density at the hydrogen bond critical points. The approach allowed to identify vanadium complexes that lead to significant changes in the hydrogen bonds indicated above, a key aspect in the understanding, development, and proposal of mechanisms of action between metal complexes and DNA.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer dinuclear Ir(III) complex activates Nrf2 and interferes with NAD(H) in cancer cells","authors":"","doi":"10.1016/j.jinorgbio.2024.112704","DOIUrl":"10.1016/j.jinorgbio.2024.112704","url":null,"abstract":"<div><p>Dinuclear complex [Ir₂(μ-L1)(η⁵-Cp*)₂Cl₂](PF₆)₂ (<strong>1</strong>) exhibits low micromolar cytotoxic activity in vitro in various human cancer cells (GI₅₀ = 1.7–3.0 μM) and outperformed its mononuclear analogue [Ir(η⁵-Cp*)Cl(L2)]PF₆ (<strong>2</strong>; GI₅₀ &gt; 40.0 μM); Cp* = pentamethylcyclopentadienyl, L1 = 4-chloro-2,6-bis[5-(pyridin-2-yl)-1,3,4-thiadiazol-2-yl]pyridine, L2 = 5-(pyridin-2-yl)-1,3,4-thiadiazol-2-amine. Compound <strong>1</strong> upregulated the Keap1/Nrf2 oxidative stress-protective pathway in the treated MV4‐11 acute myeloid leukemia cells. In connection with the redox-mediated mode of action of <strong>1</strong>, its NADH-oxidizing activity was detected in solution (¹H NMR), while NAD⁺ remained intact (with formate as a hydride source). Surprisingly, only negligible NADH oxidation was detected in the presence of the reduced glutathione and ascorbate. Following the results of in-solution experiments, NAD(H) concentration was assessed in <strong>1</strong>-treated MV4‐11 cancer cells. Besides the intracellular NADH oxidation in the presence of <strong>1</strong>, the induced oxidative stress also led to a decrease of NAD⁺, resulting in depletion of both NAD⁺/NADH coenzymes. The discussed findings provide new insight into the biochemical effects of catalytic anticancer compounds that induce cell death via a redox-mediated mode of action.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging pyrimidine hemicurcumin and Cisplatin: Synthesis, coordination chemistry, and in vitro activity assessment of a novel Pt(II) complex","authors":"","doi":"10.1016/j.jinorgbio.2024.112702","DOIUrl":"10.1016/j.jinorgbio.2024.112702","url":null,"abstract":"<div><p>In the upcoming decades, the incidence and mortality rates of cancer are expected to rise globally, with colorectal and prostate cancers among the most prevalent types. Despite advancements in molecular targeted therapy, platinum-based chemotherapies remain the cornerstone of treatment, especially for colorectal and prostate cancer, with oxaliplatin and cisplatin being extremely effective due to their DNA-targeting capabilities. In our pursuit of new platinum-based chemotherapeutics that are potentially less toxic and more effective, we have explored the combination of the Pt-binding groups of the diaminocyclohexane ring used in oxaliplatin, with the stable amino-pyrimidine hemicurcumin moiety. This new derivative exhibit improved stability in physiological conditions and increased solubility in aqueous media, demonstrating promising effects on cell proliferation of both colorectal and prostate cells. We report herein the complete synthesis and chemical characterization in solution of the new derivative [(1<em>R</em>,2<em>R</em>)-N1-(3-(4-((<em>E</em>)-2-(2-Amino-6-methylpyrimidin-4-yl)vinyl)-2-methoxyphenoxy) propyl) cyclohexane-1,2-diamine] (MPYD). Our analysis includes an examination of its acid-base equilibria, speciation and stability in physiological conditions. The synthesis and <em>in situ</em> formation of Pt(II) complexes were investigated by nuclear magnetic resonance spectroscopy, while density functional theory calculations were employed to elucidate the chemical structure in solution. Results on the biological activity were obtained through cell viability assays on different colorectal and prostate cell lines (HCT116, HT29, PC3 and LNCaP).</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0162013424002265/pdfft?md5=3433180033e6aeb67199e4fb24840072&pid=1-s2.0-S0162013424002265-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optical annealing of peroxo-ferric intermediates in CYP17A1 and product formation.","authors":"","doi":"10.1016/j.jinorgbio.2024.112701","DOIUrl":"10.1016/j.jinorgbio.2024.112701","url":null,"abstract":"<div><p>Human cytochrome P450 CYP17A1 catalyzes the hydroxylation of pregnenolone and progesterone at the C17 position, with subsequent C17-C20 bond scission, to form dehydroepiandrosterone and androstenedione respectively. The first hydroxylation reaction is faster in H₂O than in D₂O, while the second carbon‑carbon bond scission event demonstrates an inverse solvent isotope effect, which is more pronounced for 17-hydroxy pregnenolone. In order to better understand the cause of this difference, we compared the optical absorption spectra of oxygenated CYP17A1 with the four substrates (pregnenolone, progesterone, 17-hydroxy pregnenolone and 17-hydroxy progesterone) in both H₂O and D₂O. We also studied the temperature-dependent decay of the peroxo-ferric and hydroperoxo-ferric intermediates generated by cryoradiolysis of the corresponding oxygenated heme proteins at 77 K. For both pregnenolone and 17-hydroxypregnenolone, annealing of the peroxo-intermediates was observed at lower temperatures in H₂O than in D₂O. In contrast, no solvent isotope effect was detected when progesterone or 17-hydroxyprogesterone were used as substrates. These differences are attributed to their different positioning in the P450 active site with respect to the heme bound peroxo (Fe-OO⁻) moiety, which is in agreement with earlier structural and spectroscopic investigations. Analysis of the samples run in both H₂O and in D₂O, where 17-hydroxyprogesterone is the substrate, demonstrated significant (∼25%) yield of androstenedione product relative to the oxygenated starting material.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced DNA damage and anti-proliferative activity of a novel ruthenium complex with a chlorambucil-decorated ligand","authors":"","doi":"10.1016/j.jinorgbio.2024.112703","DOIUrl":"10.1016/j.jinorgbio.2024.112703","url":null,"abstract":"<div><p>Triphenylphosphine substitution reactions of [RuCl(PPh₃)₂(tpm)]Cl, <strong>1</strong>, featuring tris(pyrazolyl)methane (tpm) as ligand, with the chlorambucil-decorated pyridine ligand <strong>Py</strong>^{<strong>CA</strong>}, 3-aminopyridine (<strong>Py</strong>^{<strong>NH2</strong>}) and 4-pyridinemethanol (<strong>Py</strong>^{<strong>OH</strong>}) afforded the corresponding pyridine complexes <strong>2–4</strong> in high yields. <strong>Py</strong>^{<strong>CA</strong>} was preliminarily obtained <em>via</em> esterification of 4-pyridinemethanol with chlorambucil. The new compounds <strong>Py</strong>^{<strong>CA</strong>} and <strong>2–3</strong> were characterized by IR and multinuclear NMR spectroscopy. Additionally, the structure of <strong>3</strong> was ascertained by single crystal X-ray diffraction. The <em>in vitro</em> anti-proliferative activity of <strong>2–4</strong> and <strong>Py</strong>^{<strong>CA</strong>} was determined against a panel of cancer cell lines, outlining <strong>2</strong> as the most performing compound. Targeted studies were subsequently undertaken using <strong>2</strong> to elucidate mechanistic aspects, including the assessment of ruthenium cellular uptake, cell cycle arrest, production of reactive oxygen species (ROS), western blotting and DNA damage (comet test). Overall, data highlight that the anticancer activity provided by <strong>2</strong> primarily affects the mitochondria pathway with a potential additional contribution from DNA damage.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0162013424002277/pdfft?md5=297e1e04af4ffdab05ee142877aade6f&pid=1-s2.0-S0162013424002277-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}