Journal of Inorganic Biochemistry最新文献

{"title":"Thermodynamic and kinetic study of palladium(II) complexation with 1-methyl-2-mercaptoimidazole (methimazole) and their importance for structural design of metallodrugs","authors":"Viktorie Širůčková ,&nbsp;Přemysl Lubal ,&nbsp;Josef Hamacek ,&nbsp;Libor Kapička ,&nbsp;Lars-Ivar Elding","doi":"10.1016/j.jinorgbio.2024.112722","DOIUrl":"10.1016/j.jinorgbio.2024.112722","url":null,"abstract":"<div><div>The acidobasic and complexing properties of 1-methyl-2-mercaptoimidazole (<em>Methimazole</em>, an anti-thyroid drug) were investigated. The p<em>K</em>_a 11.49 ± 0.03 was estimated by molecular absorption spectroscopy (<em>I</em> = 0.10 M NaCl, <em>t</em> = 25.0 ± 0.1 °C). This value is in good agreement with the value 11.58 ± 0.05, obtained using the solvent-extraction technique. Theoretical (LFER and quantum chemical calculations) and experimental (¹H/¹³C NMR spectroscopy) methods confirmed that the ligand prefers to be in the thion form, and the proton dissociation takes place on the nitrogen atom. Using glass electrode potentiometry, the complexation of the Pd(II) ion by the <em>methimazole</em> ligand occurs without the participation of protons. The best chemical model considers the [Pd(HL)]²⁺, [Pd(HL)₂]²⁺ and [Pd(HL)₃]²⁺ complex species, whose stability constants were also determined using spectroscopy and capillary zone electrophoretic (CZE) measurements. The metal complexes dissociate at –log [H⁺] &gt; 7, where an uncharged palladium(II) hydroxide is formed. The formation kinetics of the palladium(II) complex with <em>methimazole</em> were studied in perchloric and hydrochloric acids (<em>I</em> = 1.00 M, <em>t</em> = 15–40 °C) and the determined rate constants and activation parameters are consistent with literature values determined for the reactions of the Pd(II) ion with thiourea derivatives. The rate constants decrease by two orders of magnitude in both media, which can be assigned to a lower tendency of the chloride ion to dissociate from the [PdCl₄]²⁻ complex species than the water molecule from the [Pd(H₂O)₄]²⁺ ion. The presented results can be utilized for the design of new Pd and Pt metallodrugs.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"262 ","pages":"Article 112722"},"PeriodicalIF":3.8,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320356","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":"Bio-molecular Fe(III) and Zn(II) complexes stimulate the interplay between PI3K/AKT1/EGFR inhibition and induce autophagy and apoptosis in epidermal skin cell cancer","authors":"Aeshah A. Awaji ,&nbsp;Heba W. Alhamdi ,&nbsp;Khulud M. Alshehri ,&nbsp;Mohammad Y. Alfaifi ,&nbsp;Ali A. Shati ,&nbsp;Serag Eldin I. Elbehairi ,&nbsp;Nancy A.-F. Radwan ,&nbsp;Hani S. Hafez ,&nbsp;Reda F.M. Elshaarawy ,&nbsp;Mary Welson","doi":"10.1016/j.jinorgbio.2024.112720","DOIUrl":"10.1016/j.jinorgbio.2024.112720","url":null,"abstract":"<div><p>This study investigated the effectiveness and safety of a hybrid thiosemicarbazone ligand (HL) and its metal complexes (Mn^II-L, Fe^III-L, Ni^II-HL, and Zn^II-HL) against epidermoid carcinoma (A-431). The results indicated that Fe^III-L is the most effective, with a high selectivity index of 8.01 and an IC₅₀ of 17.49 ± 2.12 μM for Fe^III-L. The study also revealed that the synthesized complexes effectively inhibited gene expression of the Phosphoinositide 3-kinases (PI3K), alpha serine/threonine-protein kinase (AKT1), epidermal growth factor receptor (EGFR2) axis mechanism (<em>P</em> &lt; 0.0001). Additionally, these complexes trigger a chain of events that include the inhibition of proliferating cell nuclear antigen (PCNA), transforming growth factor β1 (TGF β1), and topoisomerase II, and leading to a decrease in epidermoid cell proliferation. Furthermore, the inhibitory activity also resulted in the upregulation of caspases 3 and 9, indicating the acceleration of apoptotic markers, and the down regulation of miRNA221, suggesting a decrease in epidermoid proliferation. Molecular modeling of Fe^III-L revealed that it had the best binding energy −8.02 kcal/mol and interacted with five hydrophobic π-interactions with Val270, Gln79, Leu210, and Trp80 against AKT1. Furthermore, the binding orientation of Fe^III-L with Topoisomerase II was found to be the most stable, with a binding energy −8.25 kcal/mol. This stability was attributed to the presence of five hydrophobic π-interactions with His759, Guanin13, Cytosin8, and Ala465, and numerous ionic interactions, which were more favorable than those of doxorubicin and etoposide for new regimens of chemotherapeutic activities against skin cancer.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"262 ","pages":"Article 112720"},"PeriodicalIF":3.8,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144763","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 series of DNA targeted Cu (II) complexes containing 1,8-naphthalimide ligands: Synthesis, characterization and in vitro anticancer activity","authors":"Kehua Wang ,&nbsp;Ling Wang ,&nbsp;Zhuye Shang ,&nbsp;Xingzhi Yang ,&nbsp;Hongmei Li ,&nbsp;Xiaochun Wang ,&nbsp;Mingchang Zhu ,&nbsp;Qingtao Meng","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":"261 ","pages":"Article 112721"},"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":"Öznur Doğan Ulu ,&nbsp;Ali Kuruçay ,&nbsp;İlkay Yıldırım Gümüşhan ,&nbsp;Namık Özdemir ,&nbsp;Burhan Ateş ,&nbsp;İsmail Özdemir","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":"261 ","pages":"Article 112719"},"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":"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":"262 ","pages":"Article 112718"},"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":"261 ","pages":"Article 112707"},"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":"261 ","pages":"Article 112706"},"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":"261 ","pages":"Article 112705"},"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":"262 ","pages":"Article 112704"},"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":"260 ","pages":"Article 112702"},"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}