Adnan Zahirović , Muhamed Fočak , Selma Fetahović , Burak Tüzün , Aleksandar Višnjevac , Višnja Muzika , Maja Mitrašinović Brulić , Sabina Žero , Samra Čustović , Debbie C. Crans , Sunčica Roca
{"title":"基于腙-黄酮醇的氧化钒(V)配合物:氯衍生物的合成、表征和体内抗高血糖活性","authors":"Adnan Zahirović , Muhamed Fočak , Selma Fetahović , Burak Tüzün , Aleksandar Višnjevac , Višnja Muzika , Maja Mitrašinović Brulić , Sabina Žero , Samra Čustović , Debbie C. Crans , Sunčica Roca","doi":"10.1016/j.jinorgbio.2024.112637","DOIUrl":null,"url":null,"abstract":"<div><p>Wet synthesis approach afforded four new heteroleptic mononuclear neutral diamagnetic oxidovanadium(<em>V</em>) complexes, comprising salicylaldehyde-based 2-furoic acid hydrazones and a flavonol coligand of the general composition [VO(fla)(L-<em>ONO</em>)]. The complexes were comprehensively characterized, including chemical analysis, conductometry, infrared, electronic, and mass spectroscopy, as well as 1D <sup>1</sup>H and proton-decoupled <sup>13</sup>C(<sup>1</sup>H) NMR spectroscopy, alongside extensive 2D <sup>1</sup>H<img><sup>1</sup>H COSY, <sup>1</sup>H<img><sup>13</sup>C HMQC, and <sup>1</sup>H<img><sup>13</sup>C HMBC NMR analyses. Additionally, the quantum chemical properties of the complexes were studied using Gaussian at the B3LYP, HF, and M062X levels on the 6–31++g(d,p) basis sets. The interaction of these hydrolytically inert vanadium complexes and the BSA was investigated through spectrofluorimetric titration, synchronous fluorimetry, and FRET analysis in a temperature-dependent manner, providing valuable thermodynamic insights into van der Waals interactions and hydrogen bonding. Molecular docking was conducted to gain further understanding of the specific binding sites of the complexes to BSA. Complex <strong>2</strong>, featuring a 5-chloro-substituted salicylaldehyde component of the hydrazone, was extensively examined for its biological activity <em>in vivo</em>. The effects of complex administration on biochemical and hematological parameters were evaluated in both healthy and diabetic Wistar rats, revealing antihyperglycemic activity at millimolar concentration. Furthermore, histopathological analysis and bioaccumulation studies of the complex in the brain, kidneys, and livers of healthy and diabetic rats revealed the potential for further development of vanadium(<em>V</em>) hydrazone complexes as antidiabetic and insulin-mimetic agents.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"258 ","pages":"Article 112637"},"PeriodicalIF":3.8000,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hydrazone-flavonol based oxidovanadium(V) complexes: Synthesis, characterization and antihyperglycemic activity of chloro derivative in vivo\",\"authors\":\"Adnan Zahirović , Muhamed Fočak , Selma Fetahović , Burak Tüzün , Aleksandar Višnjevac , Višnja Muzika , Maja Mitrašinović Brulić , Sabina Žero , Samra Čustović , Debbie C. Crans , Sunčica Roca\",\"doi\":\"10.1016/j.jinorgbio.2024.112637\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Wet synthesis approach afforded four new heteroleptic mononuclear neutral diamagnetic oxidovanadium(<em>V</em>) complexes, comprising salicylaldehyde-based 2-furoic acid hydrazones and a flavonol coligand of the general composition [VO(fla)(L-<em>ONO</em>)]. The complexes were comprehensively characterized, including chemical analysis, conductometry, infrared, electronic, and mass spectroscopy, as well as 1D <sup>1</sup>H and proton-decoupled <sup>13</sup>C(<sup>1</sup>H) NMR spectroscopy, alongside extensive 2D <sup>1</sup>H<img><sup>1</sup>H COSY, <sup>1</sup>H<img><sup>13</sup>C HMQC, and <sup>1</sup>H<img><sup>13</sup>C HMBC NMR analyses. Additionally, the quantum chemical properties of the complexes were studied using Gaussian at the B3LYP, HF, and M062X levels on the 6–31++g(d,p) basis sets. The interaction of these hydrolytically inert vanadium complexes and the BSA was investigated through spectrofluorimetric titration, synchronous fluorimetry, and FRET analysis in a temperature-dependent manner, providing valuable thermodynamic insights into van der Waals interactions and hydrogen bonding. Molecular docking was conducted to gain further understanding of the specific binding sites of the complexes to BSA. Complex <strong>2</strong>, featuring a 5-chloro-substituted salicylaldehyde component of the hydrazone, was extensively examined for its biological activity <em>in vivo</em>. The effects of complex administration on biochemical and hematological parameters were evaluated in both healthy and diabetic Wistar rats, revealing antihyperglycemic activity at millimolar concentration. Furthermore, histopathological analysis and bioaccumulation studies of the complex in the brain, kidneys, and livers of healthy and diabetic rats revealed the potential for further development of vanadium(<em>V</em>) hydrazone complexes as antidiabetic and insulin-mimetic agents.</p></div>\",\"PeriodicalId\":364,\"journal\":{\"name\":\"Journal of Inorganic Biochemistry\",\"volume\":\"258 \",\"pages\":\"Article 112637\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-06-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Inorganic Biochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0162013424001612\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inorganic Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0162013424001612","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Hydrazone-flavonol based oxidovanadium(V) complexes: Synthesis, characterization and antihyperglycemic activity of chloro derivative in vivo
Wet synthesis approach afforded four new heteroleptic mononuclear neutral diamagnetic oxidovanadium(V) complexes, comprising salicylaldehyde-based 2-furoic acid hydrazones and a flavonol coligand of the general composition [VO(fla)(L-ONO)]. The complexes were comprehensively characterized, including chemical analysis, conductometry, infrared, electronic, and mass spectroscopy, as well as 1D 1H and proton-decoupled 13C(1H) NMR spectroscopy, alongside extensive 2D 1H1H COSY, 1H13C HMQC, and 1H13C HMBC NMR analyses. Additionally, the quantum chemical properties of the complexes were studied using Gaussian at the B3LYP, HF, and M062X levels on the 6–31++g(d,p) basis sets. The interaction of these hydrolytically inert vanadium complexes and the BSA was investigated through spectrofluorimetric titration, synchronous fluorimetry, and FRET analysis in a temperature-dependent manner, providing valuable thermodynamic insights into van der Waals interactions and hydrogen bonding. Molecular docking was conducted to gain further understanding of the specific binding sites of the complexes to BSA. Complex 2, featuring a 5-chloro-substituted salicylaldehyde component of the hydrazone, was extensively examined for its biological activity in vivo. The effects of complex administration on biochemical and hematological parameters were evaluated in both healthy and diabetic Wistar rats, revealing antihyperglycemic activity at millimolar concentration. Furthermore, histopathological analysis and bioaccumulation studies of the complex in the brain, kidneys, and livers of healthy and diabetic rats revealed the potential for further development of vanadium(V) hydrazone complexes as antidiabetic and insulin-mimetic agents.
期刊介绍:
The Journal of Inorganic Biochemistry is an established international forum for research in all aspects of Biological Inorganic Chemistry. Original papers of a high scientific level are published in the form of Articles (full length papers), Short Communications, Focused Reviews and Bioinorganic Methods. Topics include: the chemistry, structure and function of metalloenzymes; the interaction of inorganic ions and molecules with proteins and nucleic acids; the synthesis and properties of coordination complexes of biological interest including both structural and functional model systems; the function of metal- containing systems in the regulation of gene expression; the role of metals in medicine; the application of spectroscopic methods to determine the structure of metallobiomolecules; the preparation and characterization of metal-based biomaterials; and related systems. The emphasis of the Journal is on the structure and mechanism of action of metallobiomolecules.