S. Nandhini , M. Ranjani , G. Thiruppathi , Y.M. Jaithanya , G. Kalaiarasi , M. Ravi , G. Prabusankar , J.G. Malecki , P. Sundararaj , R. Prabhakaran
{"title":"Organoruthenium metallocycle induced mutation in gld-1 tumor suppression gene in JK1466 strain and appreciable lifespan expansion","authors":"S. Nandhini , M. Ranjani , G. Thiruppathi , Y.M. Jaithanya , G. Kalaiarasi , M. Ravi , G. Prabusankar , J.G. Malecki , P. Sundararaj , R. Prabhakaran","doi":"10.1016/j.jinorgbio.2024.112593","DOIUrl":null,"url":null,"abstract":"<div><p>Four Ru(II) complexes (<strong>A2</strong>-<strong>A5</strong>) were synthesized from the reaction of coumarin Schiff base ligands (<strong>7da2-tsc</strong>, <strong>7da3-mtsc</strong>, <strong>7da4-etsc</strong> and <strong>7da5-ptsc)</strong> with [RuHCl(CO)(PPh<sub>3</sub>)<sub>3</sub>]. The compounds were characterized by FT-IR, UV–Vis, <sup>1</sup>H, <sup>13</sup>C and <sup>31</sup>P NMR, mass spectrometry and crystallographic analysis. Calf Thymus DNA (CT-DNA) binding studies revealed the intercalative mode of binding of the complexes with DNA. The results of Bovine serum albumin (BSA) binding studies established the interaction between BSA followed static quenching mechanism. The cytotoxic effects of the complexes and the ligands were evaluated against breast (MCF-7 and MDA-MB-231) and lung carcinoma cell lines (A549 and NCI-H460) using MTT assay. Complex <strong>A4</strong> demonstrated potent cytotoxic effects on both breast and lung cancer cells. Furthermore, morphological observations and FACS analysis showed the decrease in cell density by complex <strong>A4</strong> by induced morphological changes and apoptotic body formation and cell death in both breast and lung cancer cells. Moreover, the invertebrate model <em>Caenorhabditis elegans</em> was employed to assess the <em>in vivo</em> anticancer activity of compound <strong>A4</strong>. The findings indicated that the treatment with <strong>A4</strong> reduced tumor development and significantly extended organismal lifespan by 64 % in the tumoral strain JK1466 without adversely affecting essential physiological functions of the worm. Additionally, <strong>A4</strong> demonstrated an upregulation of two crucial antioxidant defense genes. Overall, these results suggested that the compound <strong>A4</strong> can be a potential candidate with novel chemotherapeutic applications.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"257 ","pages":"Article 112593"},"PeriodicalIF":3.8000,"publicationDate":"2024-05-08","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/S0162013424001168","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Four Ru(II) complexes (A2-A5) were synthesized from the reaction of coumarin Schiff base ligands (7da2-tsc, 7da3-mtsc, 7da4-etsc and 7da5-ptsc) with [RuHCl(CO)(PPh3)3]. The compounds were characterized by FT-IR, UV–Vis, 1H, 13C and 31P NMR, mass spectrometry and crystallographic analysis. Calf Thymus DNA (CT-DNA) binding studies revealed the intercalative mode of binding of the complexes with DNA. The results of Bovine serum albumin (BSA) binding studies established the interaction between BSA followed static quenching mechanism. The cytotoxic effects of the complexes and the ligands were evaluated against breast (MCF-7 and MDA-MB-231) and lung carcinoma cell lines (A549 and NCI-H460) using MTT assay. Complex A4 demonstrated potent cytotoxic effects on both breast and lung cancer cells. Furthermore, morphological observations and FACS analysis showed the decrease in cell density by complex A4 by induced morphological changes and apoptotic body formation and cell death in both breast and lung cancer cells. Moreover, the invertebrate model Caenorhabditis elegans was employed to assess the in vivo anticancer activity of compound A4. The findings indicated that the treatment with A4 reduced tumor development and significantly extended organismal lifespan by 64 % in the tumoral strain JK1466 without adversely affecting essential physiological functions of the worm. Additionally, A4 demonstrated an upregulation of two crucial antioxidant defense genes. Overall, these results suggested that the compound A4 can be a potential candidate with novel chemotherapeutic applications.
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.