{"title":"通过化疗信息学和分子动力学模拟研究吉西他滨和 5-氟尿嘧啶对乳腺癌的协同作用","authors":"Sureba Sukumaran, Azar Zochedh, Kaliraj Chandran, Asath Bahadur Sultan, Thandavarayan Kathiresan","doi":"10.1002/qua.27498","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Co-delivering FDA-approved drugs can be less harmful and boost biological activity by targeting different protein mechanism at same time. Gemcitabine and 5-Fluorouracil (GE5F) adduct work together to destroy cancer cells and increase the efficacy in the fight against breast cancer. The basis set B3LYP/6-311 G was utilized in this investigation to improve the structure of GE5F adduct. The natural bond analysis exhibited the intermolecular interactions of the GE5F adduct. Electronic transitions were seen to be π → π*, and theoretical calculations were performed for the ultraviolet to visible spectrum. The energy gap between HOMO and LUMO was used to study the GE5F adduct's structural stability and reactivity; the computed energy gap (Δ<i>E</i>) was 3.912 eV. The Mulliken charge population was assessed and the complex structure's electrostatic potential was established. Weak interactions of the GE5F were assessed using RDG analysis, and topological aspects were investigated using LOL and ELF analysis. Investigating the GE5F adduct's adsorption, distribution, metabolism, excretion, and toxicity properties, the results confirmed that GE5F adduct comes under the safety parameters being a drug-likeness molecule. Molecular docking experiments were conducted using target proteins for breast cancer. The complex molecule had a higher binding affinity as indicated by the docking scores, which validated the better combinatorial interaction between gemcitabine and 5-Fluorouracil. With − 9.4 kcal/mol, the complex molecule's strongest binding capacity was against PARP protein, and stable confirmation was observed through molecular dynamic simulation for 100 ns with four hydrogen bond interactions. These in silico finding will pave a way for in vitro and in vivo experiments with better enhancement of FDA approved drugs.</p>\n </div>","PeriodicalId":182,"journal":{"name":"International Journal of Quantum Chemistry","volume":"124 20","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Combinatory Effect of Gemcitabine and 5-Fluorouracil Investigated Through Chemoinformatics and Molecular Dynamics Simulation Against Breast Cancer\",\"authors\":\"Sureba Sukumaran, Azar Zochedh, Kaliraj Chandran, Asath Bahadur Sultan, Thandavarayan Kathiresan\",\"doi\":\"10.1002/qua.27498\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Co-delivering FDA-approved drugs can be less harmful and boost biological activity by targeting different protein mechanism at same time. Gemcitabine and 5-Fluorouracil (GE5F) adduct work together to destroy cancer cells and increase the efficacy in the fight against breast cancer. The basis set B3LYP/6-311 G was utilized in this investigation to improve the structure of GE5F adduct. The natural bond analysis exhibited the intermolecular interactions of the GE5F adduct. Electronic transitions were seen to be π → π*, and theoretical calculations were performed for the ultraviolet to visible spectrum. The energy gap between HOMO and LUMO was used to study the GE5F adduct's structural stability and reactivity; the computed energy gap (Δ<i>E</i>) was 3.912 eV. The Mulliken charge population was assessed and the complex structure's electrostatic potential was established. Weak interactions of the GE5F were assessed using RDG analysis, and topological aspects were investigated using LOL and ELF analysis. Investigating the GE5F adduct's adsorption, distribution, metabolism, excretion, and toxicity properties, the results confirmed that GE5F adduct comes under the safety parameters being a drug-likeness molecule. Molecular docking experiments were conducted using target proteins for breast cancer. The complex molecule had a higher binding affinity as indicated by the docking scores, which validated the better combinatorial interaction between gemcitabine and 5-Fluorouracil. With − 9.4 kcal/mol, the complex molecule's strongest binding capacity was against PARP protein, and stable confirmation was observed through molecular dynamic simulation for 100 ns with four hydrogen bond interactions. These in silico finding will pave a way for in vitro and in vivo experiments with better enhancement of FDA approved drugs.</p>\\n </div>\",\"PeriodicalId\":182,\"journal\":{\"name\":\"International Journal of Quantum Chemistry\",\"volume\":\"124 20\",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-10-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Quantum Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/qua.27498\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, PHYSICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Quantum Chemistry","FirstCategoryId":"92","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/qua.27498","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
Combinatory Effect of Gemcitabine and 5-Fluorouracil Investigated Through Chemoinformatics and Molecular Dynamics Simulation Against Breast Cancer
Co-delivering FDA-approved drugs can be less harmful and boost biological activity by targeting different protein mechanism at same time. Gemcitabine and 5-Fluorouracil (GE5F) adduct work together to destroy cancer cells and increase the efficacy in the fight against breast cancer. The basis set B3LYP/6-311 G was utilized in this investigation to improve the structure of GE5F adduct. The natural bond analysis exhibited the intermolecular interactions of the GE5F adduct. Electronic transitions were seen to be π → π*, and theoretical calculations were performed for the ultraviolet to visible spectrum. The energy gap between HOMO and LUMO was used to study the GE5F adduct's structural stability and reactivity; the computed energy gap (ΔE) was 3.912 eV. The Mulliken charge population was assessed and the complex structure's electrostatic potential was established. Weak interactions of the GE5F were assessed using RDG analysis, and topological aspects were investigated using LOL and ELF analysis. Investigating the GE5F adduct's adsorption, distribution, metabolism, excretion, and toxicity properties, the results confirmed that GE5F adduct comes under the safety parameters being a drug-likeness molecule. Molecular docking experiments were conducted using target proteins for breast cancer. The complex molecule had a higher binding affinity as indicated by the docking scores, which validated the better combinatorial interaction between gemcitabine and 5-Fluorouracil. With − 9.4 kcal/mol, the complex molecule's strongest binding capacity was against PARP protein, and stable confirmation was observed through molecular dynamic simulation for 100 ns with four hydrogen bond interactions. These in silico finding will pave a way for in vitro and in vivo experiments with better enhancement of FDA approved drugs.
期刊介绍:
Since its first formulation quantum chemistry has provided the conceptual and terminological framework necessary to understand atoms, molecules and the condensed matter. Over the past decades synergistic advances in the methodological developments, software and hardware have transformed quantum chemistry in a truly interdisciplinary science that has expanded beyond its traditional core of molecular sciences to fields as diverse as chemistry and catalysis, biophysics, nanotechnology and material science.