Journal of Inorganic Biochemistry最新文献

{"title":"A structural and functional model for alkene dioxygenases","authors":"Atanu Banerjee ,&nbsp;Allison E. Creek ,&nbsp;Aramice Y.S. Malkhasian ,&nbsp;Annette M. Joseph ,&nbsp;Korine C. Lowes ,&nbsp;William W. Brennessel ,&nbsp;Andreas Omlor ,&nbsp;Volker Schünemann ,&nbsp;Priya Singh ,&nbsp;Timothy A. Jackson ,&nbsp;Ferman A. Chavez","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":"Zachary Geeraerts,&nbsp;Izumi Ishigami,&nbsp;Yuan Gao,&nbsp;Syun-Ru Yeh","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":"Jiawan Yang ,&nbsp;Xuqi Zhu ,&nbsp;Defei Kong ,&nbsp;Yi Wang ,&nbsp;Yan Yang ,&nbsp;Yunjun Liu ,&nbsp;Hui Yin","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":"Luis Soriano-Agueda ,&nbsp;Alfredo Guevara-García","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":"Eva Řezníčková ,&nbsp;Ondřej Bárta ,&nbsp;David Milde ,&nbsp;Vladimír Kryštof ,&nbsp;Pavel Štarha","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":"Matteo Mari ,&nbsp;Matteo Boniburini ,&nbsp;Marianna Tosato ,&nbsp;Francesca Zanni ,&nbsp;Filippo Bonini ,&nbsp;Francesco Faglioni ,&nbsp;Laura Cuoghi ,&nbsp;Silvia Belluti ,&nbsp;Carol Imbriano ,&nbsp;Mattia Asti ,&nbsp;Erika Ferrari","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":"Ilia G. Denisov ,&nbsp;Yelena V. Grinkova ,&nbsp;Stephen G. Sligar","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":"Alberto Gobbo ,&nbsp;Feihong Chen ,&nbsp;Stefano Zacchini ,&nbsp;Shaohua Gou ,&nbsp;Fabio Marchetti","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}

{"title":"Role of non-redox innocent ligand units in the oxidation of alcohols with H2O2 catalyzed by μ-oxido-diiron(III) bis-phenolato polypyridyl complexes","authors":"Duenpen Unjaroen ,&nbsp;Daniël R. Duijnstee ,&nbsp;Marika Di Berto Mancini ,&nbsp;Juan Chen ,&nbsp;Ronald Hage ,&nbsp;Marcel Swart ,&nbsp;Wesley R. Browne","doi":"10.1016/j.jinorgbio.2024.112698","DOIUrl":"10.1016/j.jinorgbio.2024.112698","url":null,"abstract":"<div><p>Redox non-innocent ligands hold the potential to expand the redox chemistry and activity of transition metal catalysts. The impact of the additional redox chemistry of phenol ligands in oxidation catalysis is explored here in the complex <span><math><mi>μ</mi></math></span>-oxido-diiron(III) polypyridyl (<strong>1</strong>) [(L)Fe(III)(<em>μ</em>–O)Fe(III)(L)](ClO₄)₂ (where HL is 2-(((di(pyridin-2-yl)methyl) (pyridin-2-ylmethyl) amino)methyl)phenol) and its tert-butyl substituted analog <strong>2</strong>, in which each of the Fe(III) centers is coordinated to a phenolato moiety of the ligand. Complex <strong>1</strong> was shown earlier to catalyse the oxidation of benzyl alcohols to aldehydes with H₂O₂. In particular acid was found to accelerate the reactions by removal of a lag period before catalysis initiated. Here, we use reaction monitoring with resonance Raman, UV/vis absorption and EPR spectroscopy to show that under catalytic conditions, i.e. with excess H₂O₂, rapid (<span><math><mo>&lt;</mo></math></span> 5 s) loss of the phenolato moiety occurs, resulting in the formation of an N4 ligated Fe(III) complex. This N4 coordinated complex forms a Fe(III)-OOH species, which is responsible for alcohol oxidation and over time a relatively stable oxido-bridged dinuclear Fe(III) complex forms as a resting state in the catalytic system. The main role of acid in the catalysis is shown to be to facilitate the initial coordination of H₂O₂ by driving the formation of mononuclear complexes from <strong>1</strong> and <strong>2</strong>. The data show that although the phenolato moiety imparts interesting redox properties on complex <strong>1</strong>, it does not contribute directly to the oxidation catalysis observed with H₂O₂.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0162013424002228/pdfft?md5=18cb7171ece6ffde5c665f3b2100c080&pid=1-s2.0-S0162013424002228-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044632","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":"Phenanthroline and phenyl carboxylate mixed ligand copper complexes in developing drugs to treat cancer","authors":"Carlos Y. Fernández ,&nbsp;Natalia Alvarez ,&nbsp;Analu Rocha ,&nbsp;Luis Felipe S. Mendes ,&nbsp;Antonio J. Costa-Filho ,&nbsp;Javier Ellena ,&nbsp;Alzir A. Batista ,&nbsp;Gianella Facchin","doi":"10.1016/j.jinorgbio.2024.112700","DOIUrl":"10.1016/j.jinorgbio.2024.112700","url":null,"abstract":"<div><p>The success of a classic inorganic coordination compound, Cisplatin, <em>cis</em>-[Pt(NH₃)₂Cl₂], as the first anticancer metallodrug started a field of research dedicated to discovering coordination compounds with antitumor activity, encompassing various metals. Among these, copper complexes have emerged as interesting candidates to develop drugs to treat cancer. In this work, mixed ligand complexes of Cu(II) with diimines (phenanthroline or 4-methylphenanthroline) and 3-(4-hydroxyphenyl)propanoate, phenylcarboxylate or phenylacetate were synthesized. They were characterized in the solid state, including a new crystal structure of [Cu₂(3-(4-hydroxyphenyl)propanoate)₃(phenanthroline)₂]Cl·H₂O. The obtained complexes presented a variety of stoichiometries. In solution, complexes were partially dissociated in the corresponding Cu-diimine complex. The complexes bound to the DNA by partial intercalation and groove binding, as assessed by Circular Dichroism, relative viscosity change and UV–Vis titration. The cytotoxicity of the complexes was determined in vitro on MDA-MB-231, MCF-7 (human metastatic breast adenocarcinomas, the first triple negative), MCF-10A (breast nontumoral), A549 (human lung epithelial carcinoma), and MRC-5 (human nontumoral lung epithelial cells), finding an activity higher than that of Cisplatin, although with less selectivity.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006663","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}