A new antitumor platinum(II) complex containing metformin drug: Synthesis, characterization, cellular responses, and theoretical study

IF 4 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure Pub Date : 2025-03-24 DOI:10.1016/j.molstruc.2025.142131

Neda Hosseinpour Moghadam , Sadegh Salehzadeh , Reza Kia , Nahid Shahabadi , Jamshid Karimi , Samaneh Hokmi , Samaneh Sanei Movafagh

{"title":"A new antitumor platinum(II) complex containing metformin drug: Synthesis, characterization, cellular responses, and theoretical study","authors":"Neda Hosseinpour Moghadam , Sadegh Salehzadeh , Reza Kia , Nahid Shahabadi , Jamshid Karimi , Samaneh Hokmi , Samaneh Sanei Movafagh","doi":"10.1016/j.molstruc.2025.142131","DOIUrl":null,"url":null,"abstract":"<div><div>[Pt(Met)(DMSO)Cl][PtCl<sub>3</sub>(DMSO)] complex, where Met corresponds to metformin drug, was synthesized and characterized using UV–visible spectroscopic, FT-IR spectroscopic, elemental analysis, conductivity measurements and X-ray single-crystal diffraction techniques. The binding affinity of the platinum complex with DNA was explored by adopting competitive fluorescence spectroscopy, the effect of ionic strength, and viscosity measurements. The results revealed that the platinum complex interacts with DNA via a groove binding mode.</div><div>The <em>in vitro</em> cytotoxic property of the platinum complex was evaluated in HCT-116 (human colon cancer cells). Compared with gefitinib, which is a common anticancer drug and has an IC50 value of 9.33 μg/mL on the HCT-116 cells, the IC50 value of the platinum complex synthesized in this work is 6.35 μg/mL. Thus, the present platinum complex can be potentially used for cancer chemotherapy. The nature of metal-ligand bonds in the complexes was investigated using energy decomposition analyses (EDA). The results of EDA calculations at BP86-D3/TZ2P(ZORA) level of theory confirmed that the contribution of the term ΔE<sub>elstat</sub> in ΔE<sub>int</sub> value is about 60–62 %, indicating that in all complexes the metal-ligand bonds are mostly electrostatic in nature.</div><div>Furthermore, molecular docking studies were carried out using DNA structure (PDB ID: <span><span>1BNA</span><svg><path></path></svg></span>) to clarify the molecular affinity between various optimized analogs of platinum complexes and DNA. The results show that [Pt(Met)Cl(DMSO)] can form two hydrogen bonds with DNA, while other analogs form only one hydrogen bond with DNA.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1337 ","pages":"Article 142131"},"PeriodicalIF":4.0000,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Structure","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022286025008166","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}

引用次数: 0

Abstract

[Pt(Met)(DMSO)Cl][PtCl₃(DMSO)] complex, where Met corresponds to metformin drug, was synthesized and characterized using UV–visible spectroscopic, FT-IR spectroscopic, elemental analysis, conductivity measurements and X-ray single-crystal diffraction techniques. The binding affinity of the platinum complex with DNA was explored by adopting competitive fluorescence spectroscopy, the effect of ionic strength, and viscosity measurements. The results revealed that the platinum complex interacts with DNA via a groove binding mode.

The in vitro cytotoxic property of the platinum complex was evaluated in HCT-116 (human colon cancer cells). Compared with gefitinib, which is a common anticancer drug and has an IC50 value of 9.33 μg/mL on the HCT-116 cells, the IC50 value of the platinum complex synthesized in this work is 6.35 μg/mL. Thus, the present platinum complex can be potentially used for cancer chemotherapy. The nature of metal-ligand bonds in the complexes was investigated using energy decomposition analyses (EDA). The results of EDA calculations at BP86-D3/TZ2P(ZORA) level of theory confirmed that the contribution of the term ΔE_elstat in ΔE_int value is about 60–62 %, indicating that in all complexes the metal-ligand bonds are mostly electrostatic in nature.

Furthermore, molecular docking studies were carried out using DNA structure (PDB ID: 1BNA) to clarify the molecular affinity between various optimized analogs of platinum complexes and DNA. The results show that [Pt(Met)Cl(DMSO)] can form two hydrogen bonds with DNA, while other analogs form only one hydrogen bond with DNA.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Molecular Structure 化学-物理化学

CiteScore

7.10

自引率

15.80%

发文量

2384

审稿时长

45 days

期刊介绍： The Journal of Molecular Structure is dedicated to the publication of full-length articles and review papers, providing important new structural information on all types of chemical species including: • Stable and unstable molecules in all types of environments (vapour, molecular beam, liquid, solution, liquid crystal, solid state, matrix-isolated, surface-absorbed etc.) • Chemical intermediates • Molecules in excited states • Biological molecules • Polymers. The methods used may include any combination of spectroscopic and non-spectroscopic techniques, for example: • Infrared spectroscopy (mid, far, near) • Raman spectroscopy and non-linear Raman methods (CARS, etc.) • Electronic absorption spectroscopy • Optical rotatory dispersion and circular dichroism • Fluorescence and phosphorescence techniques • Electron spectroscopies (PES, XPS), EXAFS, etc. • Microwave spectroscopy • Electron diffraction • NMR and ESR spectroscopies • Mössbauer spectroscopy • X-ray crystallography • Charge Density Analyses • Computational Studies (supplementing experimental methods) We encourage publications combining theoretical and experimental approaches. The structural insights gained by the studies should be correlated with the properties, activity and/ or reactivity of the molecule under investigation and the relevance of this molecule and its implications should be discussed.