Journal of Inorganic Biochemistry最新文献

{"title":"Impressive promiscuous biomimetic models of ascorbate, amine, and catechol oxidases","authors":"Balasubramaniam Selvakumaran,&nbsp;Mariappan Murali,&nbsp;Selvaraj Shanmugavadivel,&nbsp;Venkatesan Sindhuja,&nbsp;Velusamy Sathya","doi":"10.1016/j.jinorgbio.2024.112671","DOIUrl":"10.1016/j.jinorgbio.2024.112671","url":null,"abstract":"<div><p>Copper metalloenzymes ascorbate oxidase (AOase), amine oxidase (AmOase), and catechol oxidase (COase) possess copper(II) sites of coordination, which are trimeric, homodimeric, and dimeric, respectively. Two newly mononuclear copper(II) complexes, namely, [Cu(L)(bpy)](ClO₄) (<strong>1</strong>) and [Cu(L)(phen)](ClO₄) (<strong>2</strong>) where HL = Schiff base, have been synthesized. UV–visible, EPR and single-crystal X-ray diffraction examinations were used to validate the geometry in solution and solid state. For complex <strong>1</strong>, the metal exhibits a coordination sphere between square pyramidal and trigonal bipyramidal geometry (τ, 0.49). A positive Cu^II/^I redox potential indicates a stable switching between Cu^II and Cu^I redox states. Despite the monomeric origin, both homogeneous catalysts (<strong>1 or 2)</strong> in MeOH were found to favor three distinct chemical transformations, namely, ascorbic acid (H₂A) to dehydroascorbic acid (DA), benzylamine (Ph-CH₂-NH₂) to benzaldehyde (Ph-CHO), and 3,5-di-<em>tert</em>-butylcatechol (3,5-DTBC) to 3,5-di-<em>tert</em>-butylquinone (3,5-DTBQ) [<em>k</em>_cat: AOase, 9.6 (<strong>1</strong>) or 2.0 × 10⁶ h⁻¹(<strong>2</strong>); AmOase, 13.4 (<strong>1</strong>) or 9.4 × 10⁶ h⁻¹ (<strong>2</strong>); COase, 2.0 (<strong>1</strong>) or 1.9 × 10³ h⁻¹ (<strong>2</strong>)]. They exhibit higher levels of AOase activity as indicated by their <em>k</em>_cat values compared to the AOase enzyme. The <em>k</em>_cat values for COase activity in buffer solution [5.93 (<strong>1</strong>) or 2.95 × 10⁵ h⁻¹ (<strong>2</strong>)] are one order lower than those of the enzymes. This is because of the labile nature of the coordinated donor, the flexibility of the ligand, the simplicity of the catalyst-substrate interaction, and the positive Cu^II/^I redox potential. Interestingly, more efficient catalysis is promoted by <strong>1</strong> and <strong>2</strong> concerning that of other mono- and dicopper(II) complexes.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764701","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":"Enzymatic CO2 reduction catalyzed by natural and artificial Metalloenzymes","authors":"Yunling Deng,&nbsp;Jing-Xiang Wang,&nbsp;Barshali Ghosh,&nbsp;Yi Lu","doi":"10.1016/j.jinorgbio.2024.112669","DOIUrl":"10.1016/j.jinorgbio.2024.112669","url":null,"abstract":"<div><p>The continuously increasing level of atmospheric CO₂ in the atmosphere has led to global warming. Converting CO₂ into other carbon compounds could mitigate its atmospheric levels and produce valuable products, as CO₂ also serves as a plentiful and inexpensive carbon feedstock. However, the inert nature of CO₂ poses a major challenge for its reduction. To meet the challenge, nature has evolved metalloenzymes using transition metal ions like Fe, Ni, Mo, and W, as well as electron-transfer partners for their functions. Mimicking these enzymes, artificial metalloenzymes (ArMs) have been designed using alternative protein scaffolds and various metallocofactors like Ni, Co, Re, Rh, and Fe<img>S clusters. Both the catalytic efficiency and the scope of CO₂-reduction product of these ArMs have been improved over the past decade. This review first focuses on the natural metalloenzymes that directly reduce CO₂ by discussing their structures and active sites, as well as the proposed reaction mechanisms. It then introduces the common strategies for electrochemical, photochemical, or photoelectrochemical utilization of these native enzymes for CO₂ reduction and highlights the most recent advancements from the past five years. We also summarize principles of protein design for bio-inspired ArMs, comparing them with native enzymatic systems and outlining challenges and opportunities in enzymatic CO₂ reduction.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764700","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":"One His, two His…the emerging roles of histidine in cellular nickel trafficking","authors":"Peter T. Chivers ,&nbsp;Priyanka Basak ,&nbsp;Michael J. Maroney","doi":"10.1016/j.jinorgbio.2024.112668","DOIUrl":"10.1016/j.jinorgbio.2024.112668","url":null,"abstract":"<div><p>Biological environments present a complex array of metal-binding ligands. Metal-binding proteins have been the overwhelming focus of study because of their important and well-defined biological roles. Consequently, the presence of functional low molecular weight (LMW) metal-ligand complexes has been overlooked in terms of their roles in metallobiochemistry, particularly within cells. Recent studies in microbial systems have illuminated the different roles of L-histidine in nickel uptake, gene expression, and metalloenzyme maturation. In this focused critical review, these roles are surveyed in the context of the coordination chemistry of Ni(II) ions and the amino acid histidine, and the physico-chemical properties of nickel complexes of histidine. These complexes are fundamentally important to cellular metal homeostasis and further work is needed to fully define their contributions.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756374","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 flexible linker of 8-amino acids between the membrane binding segment and the FMN domain of cytochrome P450 reductase is necessary for optimal activity","authors":"Freeborn Rwere ,&nbsp;Naw May P. Cartee ,&nbsp;Yuting Yang ,&nbsp;Lucy Waskell","doi":"10.1016/j.jinorgbio.2024.112667","DOIUrl":"10.1016/j.jinorgbio.2024.112667","url":null,"abstract":"<div><p>The diflavin NADPH-cytochrome P450 reductase (CYPOR) plays a critical role in human cytochrome P450 (CYP) activity by sequentially delivering two electrons from NADPH to CYP enzymes during catalysis. Although electron transfer to forty-eight human CYP enzymes by the FMN hydroquinone of CYPOR is well-known, the role of the linker between the NH₂-terminus membrane-binding domain (MBD) and FMN domain in supporting the activity of P450 enzymes remains poorly understood. Here we demonstrate that a linker with at least eight residues is required to form a functional CYPOR-CYP2B4 complex. The linker has been shortened in two amino-acid increments from Phe44 to Ile57 using site directed mutagenesis. The ability of the deletion mutants to support cytochrome P450 2B4 (CYP2B4) catalysis and reduce ferric CYP2B4 was determined using an in vitro assay and stopped-flow spectrophotometry. Steady-state enzyme kinetics showed that shortening the linker by 8–14 amino acids inhibited (63–99%) the ability of CYPOR to support CYP2B4 activity and significantly increased the K_m of CYPOR for CYP2B4. In addition, the reductase mutants decreased the rate of reduction of ferric CYP2B4 (46–95%) compared to wildtype when the linker was shortened by 8–14 residues. These results indicate that a linker with a minimum length of eight residues is necessary to enable the FMN domain of reductase to interact with CYP2B4 to form a catalytically competent complex. Our study provides evidence that the length of the MBD-FMN domain linker is a major determinant of the ability of CYPOR to support CYP catalysis and drug metabolism by P450 enzymes.</p></div><div><h3>Preamble</h3><p>This manuscript is dedicated in memory of Dr. James R. Kincaid who was the doctoral advisor to Dr. Freeborn Rwere and a longtime collaborator and friend of Dr. Lucy Waskell. Dr. James R. Kincaid was a distinguished professor of chemistry specializing in resonance Raman (rR) studies of heme proteins. He inspired Dr. Rwere (a Zimbabwean native) and three other Zimbabweans (Dr. Remigio Usai, Dr. Daniel Kaluka and Ms. Munyaradzi E. Manyumwa) to use lasers to document subtle changes occurring at heme active site of globin proteins (myoglobin and hemoglobin) and cytochrome P450 enzymes. Dr. Rwere appreciate his contributions to the development of talented Black scientists from Africa.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141728650","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":"TAR RNA selective targeting ruthenium(II) complexes as HIV-1 reverse transcriptase inhibitors: On exploring structure-activity relationships of multiple positions","authors":"Meng Liu,&nbsp;Dan-Dan Xie,&nbsp;Yuan-Xiao Guo,&nbsp;Run-Yu Zhao,&nbsp;Fu-Dan Liu,&nbsp;Hongbin Zhang,&nbsp;Feng Gao","doi":"10.1016/j.jinorgbio.2024.112664","DOIUrl":"10.1016/j.jinorgbio.2024.112664","url":null,"abstract":"<div><p>HIV-1 reverse transcriptase (RT) inhibitors play a crucial role in the treatment of HIV by preventing the activity of the enzyme responsible for the replication of the virus. The HIV-1 Tat protein binds to transactivation response (TAR) RNA and recruits host factors to stimulate HIV-1 transcription. We have created a small library consisting of 4 × 6 polypyridyl Ru(II) complexes that selectively bind to TAR RNA, with targeting groups specific to HIV-1 TAR RNA. The molecule design was conducted by introducing hydroxyl or methoxy groups into an established potent TAR binder. The potential TAR binding ability was analysis from nature charge population and electrostatic potential by quantum chemistry calculations. Key modifications were found to be R₁ and R₃ groups. The most potent and selective TAR RNA binder was <strong>a3</strong> with R₁ = OH, R₂ = H and R₃ = Me. Through molecular recognition of hydrogen bonds and electrostatic attraction, they were able to firmly and selectively bind HIV-1 TAR RNA. Furthermore, they efficiently obstructed the contact between TAR RNA and Tat protein, and inhibited the reverse transcription activity of HIV-1 RT. The polypyridyl Ru(II) complexes were chemical and photo-stable, and sensitive and selective spectroscopic responses to TAR RNA. They exhibited little toxicity towards normal cells. Hence, this study might offer significant drug design approaches for researching AIDS and other illnesses associated with RT, including HCV, EBOV, and SARS-CoV-2. Moreover, it could contribute to fundamental research on the interactions of inorganic transition metal complexes with biomolecules.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632221","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":"8th Georgian Bay International Conference on Bioinorganic Chemistry (CanBIC-8)","authors":"Martin Stillman,&nbsp;John Dawson,&nbsp;Nagao Kobayashi,&nbsp;Zhifeng Ding","doi":"10.1016/j.jinorgbio.2024.112662","DOIUrl":"10.1016/j.jinorgbio.2024.112662","url":null,"abstract":"","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141703527","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":"Solution studies, synthesis and antibacterial activity of Ga(III) complexes with bis-kojate derivatives","authors":"L. More O'Ferrall ,&nbsp;A. Fantasia ,&nbsp;K. Chan ,&nbsp;L.M. Teixeira ,&nbsp;K. Kavanagh ,&nbsp;C. O'Connor ,&nbsp;M.A. Santos ,&nbsp;S. Chaves ,&nbsp;V.M. Nurchi ,&nbsp;G. Crisponi ,&nbsp;M.A. Zoroddu ,&nbsp;D.M. Griffith ,&nbsp;R. Cappai","doi":"10.1016/j.jinorgbio.2024.112663","DOIUrl":"10.1016/j.jinorgbio.2024.112663","url":null,"abstract":"<div><p>Given the recognized major problem of microbial drug resistance for human health, new metal-based drugs have been currently explored for their antimicrobial properties, including gallium-based compounds as potential metallophores that could perturb Fe’s interactions with proteins. Herein we have designed and synthesized two bis-kojate ligands (named L4 and L6) and studied their Ga(III) complexes for their physico-chemical and biological properties. In particular a detailed study of their complexation properties in aqueous solution, showed equilibrium models with formation of quite stable dinuclear 2:3 metal:ligand complexes, though with different stability. Solid state complexes were also prepared and characterized and complementary DFT studies indicated that [Ga₂(L4)₃] complex, with higher stability, seems to adopt a three-ligand bridging conformation, while that for L6 adopt a one ligand bridging conformation. Preliminary investigation of the antibacterial activity of these gallium complexes showed antipseudomonal activity, which appeared higher for the complex with L4, a feature of potential interest for the scientific community.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0162013424001879/pdfft?md5=e87200d579df0157343e826db2c097b2&pid=1-s2.0-S0162013424001879-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141637040","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":"Three Ru(II) complexes modulate the antioxidant transcription factor Nrf2 to overcome cisplatin resistance","authors":"Lanmei Chen ,&nbsp;Hong Tang ,&nbsp;Tianling Hu ,&nbsp;Jie Wang ,&nbsp;Qianqian Ouyang ,&nbsp;Xufeng Zhu ,&nbsp;Rui Wang ,&nbsp;Wenyong Huang ,&nbsp;Zunnan Huang ,&nbsp;Jincan Chen","doi":"10.1016/j.jinorgbio.2024.112666","DOIUrl":"10.1016/j.jinorgbio.2024.112666","url":null,"abstract":"<div><p>Here, we designed, synthesized and characterized three new cyclometalated Ru(II) complexes, [Ru(phen)₂(1-(4-Ph-Ph)-IQ)]⁺ (phen = 1,10-phenanthroline, IQ = isoquinoline, RuIQ9), [Ru(phen)₂(1-(4-Ph-Ph)-7-OCH₃-IQ)]⁺ (RuIQ10), and [Ru(phen)₂(1-(4-Ph-Ph)-6,7-(OCH₃)₂-IQ)]⁺ (RuIQ11). The cytotoxicity experiments conducted on both 2D and 3D multicellular tumor spheroids (MCTSs) indicated that complexes RuIQ9–11 exhibited notably higher cytotoxicity against A549 and A549/DDP cells when compared to the ligands and precursor compounds as well as clinical cisplatin. Moreover, the Ru(II) complexes displayed low toxicity when tested on normal HBE cells in vitro and exposed to zebrafish embryos in vivo. In addition, complexes RuIQ9–11 could inhibit A549 and A549/DDP cell migration and proliferation by causing cell cycle arrest, mitochondrial dysfunction, and elevating ROS levels to induce apoptosis in these cells. Mechanistic studies revealed that RuIQ9–11 could suppress the expression of Nrf2 and its downstream antioxidant protein HO-1 by inhibiting Nrf2 gene transcription in drug-resistant A549/DDP cells. Simultaneously, they inhibited the expression of efflux proteins MRP1 and p-gp in drug-resistant cells, ensuring the accumulation of the complexes within the cells. This led to an increase in intracellular ROS levels in drug-resistant cells, ultimately causing damage and cell death, thus overcoming cisplatin resistance. More importantly, RuIQ11 could effectively inhibit the migration and proliferation of drug-resistant cells within zebrafish, addressing the issue of cisplatin resistance. Accordingly, the prepared Ru(II) complexes possess significant potential for development as highly effective and low-toxicity lung cancer therapeutic agents to overcome cisplatin resistance.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141637041","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":"Covalent versus noncovalent attachments of [FeFe]‑hydrogenase models onto carbon nanotubes for aqueous hydrogen evolution reaction","authors":"Yan Gao,&nbsp;Shao-Jie Wang,&nbsp;Zhen Guo,&nbsp;Yan-Zhong Wang,&nbsp;Yong-Ping Qu,&nbsp;Pei-Hua Zhao","doi":"10.1016/j.jinorgbio.2024.112665","DOIUrl":"10.1016/j.jinorgbio.2024.112665","url":null,"abstract":"<div><p>In an effort to develop the biomimetic chemistry of [FeFe]‑hydrogenases for catalytic hydrogen evolution reaction (HER) in aqueous environment, we herein report the integrations of diiron dithiolate complexes into carbon nanotubes (CNTs) through three different strategies and compare the electrochemical HER performances of the as-resulted 2Fe2S/CNT hybrids in neutral aqueous medium. That is, three new diiron dithiolate complexes [{(<em>μ</em>-SCH₂)₂N(C₆H₄CH₂C(<em>O</em>)R)}Fe₂(CO)₆] (R = N-oxylphthalimide (<strong>1</strong>), NHCH₂pyrene (<strong>2</strong>), and NHCH₂Ph (<strong>3</strong>)) were prepared and could be further grafted covalently to CNTs via an amide bond (this 2Fe2S/CNT hybrid is labeled as <strong>H1</strong>) as well as immobilized noncovalently to CNTs via π-π stacking interaction (<strong>H2</strong>) or via simple physisorption (<strong>H3</strong>). Meanwhile, the molecular structures of <strong>1</strong>–<strong>3</strong> are determined by elemental analysis and spectroscopic as well as crystallographic techniques, whereas the structures and morphologies of <strong>H1</strong>-<strong>H3</strong> are characterized by various spectroscopies and scanning electronic microscopy. Further, the electrocatalytic HER activity trend of <strong>H1</strong> &gt; <strong>H2</strong> ≈ <strong>H3</strong> is observed in 0.1 M phosphate buffer solution (pH = 7) through different electrochemical measurements, whereas the degradation processes of <strong>H1</strong>-<strong>H3</strong> lead to their electrocatalytic deactivation in the long-term electrolysis as proposed by <em>post operando</em> analysis. Thus, this work is significant to extend the potential application of carbon electrode materials engineered with diiron molecular complexes as heterogeneous HER electrocatalysts for water splitting to hydrogen.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629860","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":"Co-targeting CDK 4/6 and C-MYC/STAT3/CCND1 axis and inhibition of tumorigenesis and epithelial-mesenchymal-transition in triple negative breast cancer by Pt(II) complexes bearing NH3 as trans-co-ligand","authors":"Zhimin Lv ,&nbsp;Amjad Ali ,&nbsp;Na Wang ,&nbsp;Haojie Ren ,&nbsp;Lijing Liu ,&nbsp;Fufu Yan ,&nbsp;Man Shad ,&nbsp;Huifang Hao ,&nbsp;Yongmin Zhang ,&nbsp;Faiz-Ur Rahman","doi":"10.1016/j.jinorgbio.2024.112661","DOIUrl":"10.1016/j.jinorgbio.2024.112661","url":null,"abstract":"<div><p>In search of potential anticancer agents, we synthesized SNO-donor salicylaldimine main ligand-based Pt(II) complexes bearing NH₃ as co-ligand at <em>trans</em>-position (<strong>C1-C6)</strong>. These complexes showed similarity in structure with transplatin as the two N donor atoms of the main ligand and NH₃ co-ligand were coordinated to Pt in <em>trans</em> position to each other. Each complex with different substituents on the main ligand was characterized thoroughly by detailed spectroscopic and spectrophotometric methods. Four of these complexes were studied in solid state by single crystal X-ray analysis. The stability of reference complex <strong>C1</strong> was measured in solution state in DMSO‑<em>d</em>₆ or its mixture with D₂O using ¹H NMR methods. These complexes were further investigated for their anticancer activity in triple-negative-breast (TNBC) cells including MDA-MB-231, MDA-MB-468 and MDA-MB-436 cells. All these complexes showed satisfactory cytotoxic effect as revealed by the MTT results. Importantly, the highly active complex <strong>C4</strong> anticancer effect was compared to the standard chemotherapeutic agents including cisplatin, oxaliplatin and 5-fluorouracil (5-FU). Functionally, <strong>C4</strong> suppressed invasion, spheroids formation ability and clonogenic potential of cancer cells. <strong>C4</strong> showed synergistic anticancer effect when used in combination with palbociclib, JQ1 and paclitaxel in TNBC cells. Mechanistically, <strong>C4</strong> inhibited cyclin-dependent kinase (CDK)4/6 pathway and targeted the expressions of MYC/STAT3/CCND1/CNNE1 axis. Furthermore, <strong>C4</strong> suppressed the EMT signaling pathway that suggested a role of <strong>C4</strong> in the inhibition of TNBC metastasis. Our findings may pave further in detailed mechanistic study on these complexes as potential chemotherapeutic agents in different types of human cancers.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629884","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}