{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T03:31:11Z","timestamp":1790134271474,"version":"4.0.1"},"reference-count":94,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,5,16]],"date-time":"2018-05-16T00:00:00Z","timestamp":1526428800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,5,16]],"date-time":"2018-05-16T00:00:00Z","timestamp":1526428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>New ruthenium(II) complexes were synthesised and characterized by various spectro analytical techniques. The structure of the complexes <jats:bold>3<\/jats:bold> and <jats:bold>4<\/jats:bold> has been confirmed by X-ray crystallography. The complexes were subjected to study their anti-oxidant profile and were exhibited significantly greater <jats:italic>in vitro<\/jats:italic> DPPH radical scavenging activity than vitamin C. We found that complexes <jats:bold>1\u20134<\/jats:bold> confered tolerance to oxidative stress and extend the mean lifespan of <jats:italic>mev-1<\/jats:italic> mutant worms and wild-type <jats:italic>Caenorhabditis elegans<\/jats:italic>. Further, mechanistic study and reporter gene expression analysis revealed that Ru(<jats:italic>\u019e<\/jats:italic><jats:sup>6<\/jats:sup><jats:italic>-p<\/jats:italic>-cymene) complexes maintained the intracellular redox status and offers stress resistance through activating JNK-1\/DAF-16 signaling axis and possibly by other antioxidant response pathway. Notably, complex <jats:bold>3<\/jats:bold> and <jats:bold>4<\/jats:bold> ameliorates the polyQ (a Huntington\u2019s disease associated protein) mediated proteotoxicity and related behavioural deficits in Huntington\u2019s disease models of <jats:italic>C. elegans<\/jats:italic>. From these observations, we hope that new Ru(<jats:italic>\u019e<\/jats:italic><jats:sup>6<\/jats:sup><jats:italic>-p<\/jats:italic>-cymene) complexes could be further considered as a potential drug to retard aging and age-related neurodegenerative diseases.<\/jats:p>","DOI":"10.1038\/s41598-018-25984-7","type":"journal-article","created":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T13:18:28Z","timestamp":1525958308000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Organoruthenium(II) Complexes Ameliorates Oxidative Stress and Impedes the Age Associated Deterioration in Caenorhabditis elegans through JNK-1\/DAF-16 Signalling"],"prefix":"10.1038","volume":"8","author":[{"given":"G.","family":"Devagi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7840-4716","authenticated-orcid":false,"given":"A.","family":"Mohankumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Shanmugam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Nivitha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Dallemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Kalaivani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Sundararaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8941-3295","authenticated-orcid":false,"given":"R.","family":"Prabhakaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,5,16]]},"reference":[{"key":"25984_CR1","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1126\/science.1124514","volume":"311","author":"T Gidalevitz","year":"2006","unstructured":"Gidalevitz, T. Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science (80-.). 311, 1471\u20131474 (2006).","journal-title":"Science (80-.)."},{"key":"25984_CR2","first-page":"1","volume":"2017","author":"Z Liu","year":"2017","unstructured":"Liu, Z., Zhou, T., Ziegler, A. C., Dimitrion, P. & Zuo, L. Oxidative stress in neurodegenerative diseases: From molecular mechanisms to clinical applications. Oxid. Med. Cell. Longev. 2017, 1\u201311 (2017).","journal-title":"Oxid. Med. Cell. Longev."},{"key":"25984_CR3","doi-asserted-by":"crossref","unstructured":"Manoharan, S. et al. The Role of reactive oxygen species in the pathogenesis of Alzheimer\u2019s disease, Parkinson\u2019s disease, and Huntington\u2019s disease: A mini review. Oxidative Medicine and Cellular Longevity 2016, (2016).","DOI":"10.1155\/2016\/8590578"},{"key":"25984_CR4","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1016\/j.exger.2006.06.038","volume":"41","author":"JJ Collins","year":"2006","unstructured":"Collins, J. J., Evason, K. & Kornfeld, K. Pharmacology of delayed aging and extended lifespan of Caenorhabditis elegans. Exp. Gerontol. 41, 1032\u20131039 (2006).","journal-title":"Exp. Gerontol."},{"key":"25984_CR5","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1038\/nature07216","volume":"454","author":"J Vijg","year":"2008","unstructured":"Vijg, J. & Campisi, J. Puzzles, promises and a cure for ageing. Nature 454, 1065\u20131071 (2008).","journal-title":"Nature"},{"key":"25984_CR6","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1016\/j.ccr.2006.11.017","volume":"251","author":"L Ronconi","year":"2007","unstructured":"Ronconi, L. & Sadler, P. J. Using coordination chemistry to design new medicines. Coordination Chemistry Reviews 251, 1633\u20131648 (2007).","journal-title":"Coordination Chemistry Reviews"},{"key":"25984_CR7","doi-asserted-by":"crossref","unstructured":"Reedijk, J. Platinum anticancer coordination compounds: Study of DNA binding inspires new drug design. Eur. J. Inorg. Chem. 1303\u20131312 (2009).","DOI":"10.1002\/ejic.200900054"},{"key":"25984_CR8","doi-asserted-by":"crossref","unstructured":"Yan, Y. K., Melchart, M., Habtemariam, A. & Sadler, P. J. Organometallic chemistry, biology and medicine: ruthenium arene anticancer complexes. Chem. Commun. 4764 (2005).","DOI":"10.1039\/b508531b"},{"key":"25984_CR9","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1595\/147106708X255987","volume":"52","author":"BJ Reedijk","year":"2008","unstructured":"Reedijk, B. J. Metal-ligand exchange kinetics in platinum and ruthenium complexes. Platin. Met. Rev. 52, 2\u201311 (2008).","journal-title":"Platin. Met. Rev."},{"key":"25984_CR10","doi-asserted-by":"crossref","unstructured":"Dyson, P. J. & Sava, G. Metal-based antitumour drugs in the post genomic era. Dalt. Trans. 1929 (2006).","DOI":"10.1039\/b601840h"},{"key":"25984_CR11","doi-asserted-by":"publisher","first-page":"704","DOI":"10.2533\/chimia.2007.704","volume":"61","author":"SJ Dougan","year":"2007","unstructured":"Dougan, S. J. & Sadler, P. J. The Design of organometallic ruthenium arene anticancer agents. Chim. Int. J. Chem. 61, 704\u2013715 (2007).","journal-title":"Chim. Int. J. Chem."},{"key":"25984_CR12","doi-asserted-by":"publisher","first-page":"698","DOI":"10.2533\/chimia.2007.698","volume":"61","author":"PJ Dyson","year":"2007","unstructured":"Dyson, P. J. Systematic design of a targeted organometallic antitumour drug in pre-clinical development. Chim. Int. J. Chem. 61, 698\u2013703 (2007).","journal-title":"Chim. Int. J. Chem."},{"key":"25984_CR13","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1039\/B916860P","volume":"39","author":"G S\u00fcss-Fink","year":"2010","unstructured":"S\u00fcss-Fink, G. Arene ruthenium complexes as anticancer agents. Dalton Trans. 39, 1673\u20131688 (2010).","journal-title":"Dalton Trans."},{"key":"25984_CR14","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/978-3-642-13185-1_2","volume":"32","author":"AM Pizarro","year":"2010","unstructured":"Pizarro, A. M., Habtemariam, A. & Sadler, P. J. Activation mechanisms for organometallic anticancer complexes. Top. Organomet. Chem. 32, 21\u201356 (2010).","journal-title":"Top. Organomet. Chem."},{"key":"25984_CR15","doi-asserted-by":"publisher","first-page":"3616","DOI":"10.1021\/jm010051m","volume":"44","author":"RE Morris","year":"2001","unstructured":"Morris, R. E. et al. Inhibition of cancer cell growth by ruthenium(II) arene complexes. J. Med. Chem. 44, 3616\u20133621 (2001).","journal-title":"J. Med. Chem."},{"key":"25984_CR16","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1038\/sj.bjc.6600290","volume":"86","author":"RE Aird","year":"2002","unstructured":"Aird, R. E. et al. In vitro and in vivo activity and cross resistance profiles of novel ruthenium(II) organometallic arene complexes in human ovarian cancer. Br. J. Cancer 86, 1652\u20131657 (2002).","journal-title":"Br. J. Cancer"},{"key":"25984_CR17","doi-asserted-by":"publisher","first-page":"11544","DOI":"10.1021\/bi034933u","volume":"42","author":"O Novakova","year":"2003","unstructured":"Novakova, O. et al. DNA interactions of monofunctional organometallic ruthenium(II) antitumour complexes in cell-free media. Biochemistry 42, 11544\u201311554 (2003).","journal-title":"Biochemistry"},{"key":"25984_CR18","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1021\/ja027719m","volume":"125","author":"H Chen","year":"2003","unstructured":"Chen, H., Parkinson, J. A., Morris, R. E. & Sadler, P. J. Highly selective binding of organometallic ruthenium ethylenediamine complexes to nucleic acids: Novel recognition mechanisms. J. Am. Chem. Soc. 125, 173\u2013186 (2003).","journal-title":"J. Am. Chem. Soc."},{"key":"25984_CR19","doi-asserted-by":"publisher","first-page":"4509","DOI":"10.1021\/ic025538f","volume":"41","author":"F Wang","year":"2002","unstructured":"Wang, F. et al. Reactions of a ruthenium(II) arene antitumor complex with cysteine and methionine. Inorg. Chem. 41, 4509\u20134523 (2002).","journal-title":"Inorg. Chem."},{"key":"25984_CR20","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s00775-004-0621-5","volume":"10","author":"F Wang","year":"2005","unstructured":"Wang, F., Bella, J., Parkinson, J. A. & Sadler, P. J. Competitive reactions of a ruthenium arene anticancer complex with histidine, cytochrome c and an oligonucleotide. J. Biol. Inorg. Chem. 10, 147\u2013155 (2005).","journal-title":"J. Biol. Inorg. Chem."},{"key":"25984_CR21","doi-asserted-by":"publisher","first-page":"17734","DOI":"10.1021\/ja053387k","volume":"127","author":"F Wang","year":"2005","unstructured":"Wang, F., Xu, J., Habtemariam, A., Bella, J. & Sadler, P. J. Competition between glutathione and guanine for a ruthenium(II) arene anticancer complex: Detection of a sulfenato intermediate. J. Am. Chem. Soc. 127, 17734\u201317743 (2005).","journal-title":"J. Am. Chem. Soc."},{"key":"25984_CR22","doi-asserted-by":"publisher","first-page":"5173","DOI":"10.1002\/chem.200400640","volume":"10","author":"R Fern\u00e1ndez","year":"2004","unstructured":"Fern\u00e1ndez, R., Melchart, M., Habtemariam, A., Parsons, S. & Sadler, P. J. Use of chelating ligands to tune the reactive site of half-sandwich ruthenium(II)-arene anticancer complexes. Chem. - A Eur. J. 10, 5173\u20135179 (2004).","journal-title":"Chem. - A Eur. J."},{"key":"25984_CR23","doi-asserted-by":"publisher","first-page":"6858","DOI":"10.1021\/jm060596m","volume":"49","author":"A Habtemariam","year":"2006","unstructured":"Habtemariam, A. et al. Structure-activity relationships for cytotoxic ruthenium(II) arene complexes containing N,N-, N,O-, and O,O-chelating ligands. J. Med. Chem. 49, 6858\u20136868 (2006).","journal-title":"J. Med. Chem."},{"key":"25984_CR24","doi-asserted-by":"publisher","first-page":"9006","DOI":"10.1021\/ic061008y","volume":"45","author":"HA Wee","year":"2006","unstructured":"Wee, H. A. et al. Development of organometallic ruthenium-arene anticancer drugs that resist hydrolysis. Inorg. Chem. 45, 9006\u20139013 (2006).","journal-title":"Inorg. Chem."},{"key":"25984_CR25","doi-asserted-by":"publisher","unstructured":"Vock, C. A., Renfrew, A. K., Scopelliti, R., Juillerat-Jeanneret, L. & Dyson, P. J. Influence of the diketonato ligand on the cytotoxicities of [Ru(\u03b76-p-cymene)-(R2acac)(PTA)]\u2009+\u2009complexes (PTA\u2009=\u20091,3,5-triaza-7-phosphaadamantane). Eur. J. Inorg. Chem. 1661\u20131671 https:\/\/doi.org\/10.1002\/ejic.200701291 (2008).","DOI":"10.1002\/ejic.200701291"},{"key":"25984_CR26","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1021\/jm801276a","volume":"52","author":"A Valentini","year":"2009","unstructured":"Valentini, A. et al. Synthesis, oxidant properties, and antitumoral effects of a heteroleptic palladium(II) complex of curcumin on human prostate cancer cells. J. Med. Chem. 52, 484\u2013491 (2009).","journal-title":"J. Med. Chem."},{"key":"25984_CR27","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1016\/j.jinorgbio.2007.03.006","volume":"101","author":"D Pucci","year":"2007","unstructured":"Pucci, D. et al. Curcumin and cyclopalladated complexes: A recipe for bifunctional biomaterials. J. Inorg. Biochem. 101, 1013\u20131022 (2007).","journal-title":"J. Inorg. Biochem."},{"key":"25984_CR28","doi-asserted-by":"publisher","first-page":"3043","DOI":"10.1016\/j.bmc.2009.03.016","volume":"17","author":"E Ferrari","year":"2009","unstructured":"Ferrari, E. et al. Synthesis, cytotoxic and combined cDDP activity of new stable curcumin derivatives. Bioorganic Med. Chem. 17, 3043\u20133052 (2009).","journal-title":"Bioorganic Med. Chem."},{"key":"25984_CR29","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.jinorgbio.2008.12.001","volume":"103","author":"Y-M Song","year":"2009","unstructured":"Song, Y.-M. et al. Syntheses, characterization and biological activities of rare earth metal complexes with curcumin and 1,10-phenanthroline-5,6-dione. J. Inorg. Biochem. 103, 396\u2013400 (2009).","journal-title":"J. Inorg. Biochem."},{"key":"25984_CR30","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1016\/j.bcp.2008.08.008","volume":"76","author":"P Anand","year":"2008","unstructured":"Anand, P. et al. Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem. Pharmacol. 76, 1590\u20131611 (2008).","journal-title":"Biochem. Pharmacol."},{"key":"25984_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-0-387-46401-5_1","volume":"595","author":"BB Aggarwal","year":"2007","unstructured":"Aggarwal, B. B., Sundaram, C., Malani, N. & Ichikawa, H. Curcumin: The Indian solid gold. Advances in Experimental Medicine and Biology 595, 1\u201375 (2007).","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"25984_CR32","doi-asserted-by":"publisher","first-page":"5892","DOI":"10.1074\/jbc.M404751200","volume":"280","author":"F Yang","year":"2005","unstructured":"Yang, F. et al. Curcumin inhibits formation of amyloid \u03b2 oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J. Biol. Chem. 280, 5892\u20135901 (2005).","journal-title":"J. Biol. Chem."},{"key":"25984_CR33","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1111\/j.1471-4159.2007.04613.x","volume":"102","author":"M Garcia-Alloza","year":"2007","unstructured":"Garcia-Alloza, M., Borrelli, L. A., Rozkalne, A., Hyman, B. T. & Bacskai, B. J. Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model. J. Neurochem. 102, 1095\u20131104 (2007).","journal-title":"J. Neurochem."},{"key":"25984_CR34","doi-asserted-by":"publisher","first-page":"8245","DOI":"10.1021\/ic700394r","volume":"46","author":"F Marchetti","year":"2007","unstructured":"Marchetti, F. et al. Areneruthenium(II) 4-acyl-5-pyrazolonate derivatives: Coordination chemistry, redox properties, and reactivity. Inorg. Chem. 46, 8245\u20138257 (2007).","journal-title":"Inorg. Chem."},{"key":"25984_CR35","doi-asserted-by":"publisher","first-page":"31","DOI":"10.2174\/1389557043487484","volume":"4","author":"H Beraldo","year":"2004","unstructured":"Beraldo, H. & Gambino, D. The Wide Pharmacological Versatility of Semicarbazones, Thiosemicarbazones and Their Metal Complexes. Mini-Reviews Med. Chem. 4, 31\u201339 (2004).","journal-title":"Mini-Reviews Med. Chem."},{"key":"25984_CR36","doi-asserted-by":"publisher","first-page":"5271","DOI":"10.1021\/jm900552r","volume":"52","author":"Y Yu","year":"2009","unstructured":"Yu, Y. et al. Thiosemicarbazones from the old to new: Iron chelators that are more than just ribonucleotide reductase inhibitors. Journal of Medicinal Chemistry 52, 5271\u20135294 (2009).","journal-title":"Journal of Medicinal Chemistry"},{"key":"25984_CR37","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.4155\/fmc.09.80","volume":"1","author":"DS Kalinowski","year":"2009","unstructured":"Kalinowski, D. S., Quach, P. & Richardson, D. R. Thiosemicarbazones: the new wave in cancer treatment. Future Med. Chem. 1, 1143\u20131151 (2009).","journal-title":"Future Med. Chem."},{"key":"25984_CR38","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1021\/jm010252q","volume":"45","author":"S Ren","year":"2002","unstructured":"Ren, S. et al. Synthesis, biological evaluation, and quantitative structure-activity relationship analysis of new Schiff bases of hydroxysemicarbazide as potential antitumor agents. J Med Chem 45, 410\u2013419 (2002).","journal-title":"J Med Chem"},{"key":"25984_CR39","doi-asserted-by":"publisher","first-page":"3191","DOI":"10.1021\/jm800861c","volume":"52","author":"MD Hall","year":"2009","unstructured":"Hall, M. D. et al. Synthesis, activity, and pharmacophore development for isatin-\u03b2- thiosemicarbazones with selective activity toward multidrug-resistant cells. J. Med. Chem. 52, 3191\u20133204 (2009).","journal-title":"J. Med. Chem."},{"key":"25984_CR40","doi-asserted-by":"publisher","first-page":"5878","DOI":"10.1021\/jm2006047","volume":"54","author":"MD Hall","year":"2011","unstructured":"Hall, M. D. et al. Synthesis and structure-activity evaluation of isatin-\u03b2- thiosemicarbazones with improved selective activity toward multidrug-resistant cells expressing P-glycoprotein. J. Med. Chem. 54, 5878\u20135889 (2011).","journal-title":"J. Med. Chem."},{"key":"25984_CR41","doi-asserted-by":"publisher","first-page":"7242","DOI":"10.1021\/jm060712l","volume":"49","author":"S Adsule","year":"2006","unstructured":"Adsule, S. et al. Novel Schiff base copper complexes of quinoline-2 carboxaldehyde as proteasome inhibitors in human prostate cancer cells. J. Med. Chem. 49, 7242\u20137246 (2006).","journal-title":"J. Med. Chem."},{"key":"25984_CR42","doi-asserted-by":"publisher","first-page":"3716","DOI":"10.1021\/jm070445z","volume":"50","author":"DS Kalinowski","year":"2007","unstructured":"Kalinowski, D. S. et al. Design, synthesis, and characterization of novel iron chelators: Structure-activity relationships of the 2-benzoylpyridine thiosemicarbazone series and their 3-nitrobenzoyl analogues as potent antitumor agents. J. Med. Chem. 50, 3716\u20133729 (2007).","journal-title":"J. Med. Chem."},{"key":"25984_CR43","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1021\/jm801585u","volume":"52","author":"DR Richardson","year":"2009","unstructured":"Richardson, D. R. et al. 2-Acetylpyridine thiosemicarbazones are potent iron chelators and antiproliferative agents: Redox activity, iron complexation and characterization of their antitumor activity. J. Med. Chem. 52, 1459\u20131470 (2009).","journal-title":"J. Med. Chem."},{"key":"25984_CR44","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1038\/nature08980","volume":"464","author":"CJ Kenyon","year":"2010","unstructured":"Kenyon, C. J. The genetics of ageing. Nature 464, 504\u2013512 (2010).","journal-title":"Nature"},{"key":"25984_CR45","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1016\/j.exger.2006.05.020","volume":"41","author":"A Mukhopadhyay","year":"2006","unstructured":"Mukhopadhyay, A., Oh, S. W. & Tissenbaum, H. A. Worming pathways to and from DAF-16\/FOXO. Exp. Gerontol. 41, 928\u2013934 (2006).","journal-title":"Exp. Gerontol."},{"key":"25984_CR46","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jorganchem.2017.03.023","volume":"838","author":"G Devagi","year":"2017","unstructured":"Devagi, G. et al. Caenorhabditis elegans as a model for exploring the efficacy of synthesized organoruthenium complexes for aging and Alzheimer\u2019s disease a neurodegenerative disorder: A systematic approach. J. Organomet. Chem. 838, 12\u201323 (2017).","journal-title":"J. Organomet. Chem."},{"key":"25984_CR47","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/S0959-440X(99)00048-2","volume":"10","author":"JI Clark","year":"2000","unstructured":"Clark, J. I. & Muchowski, P. J. Small heat-shock proteins and their potential role in human disease. Current Opinion in Structural Biology 10, 52\u201359 (2000).","journal-title":"Current Opinion in Structural Biology"},{"key":"25984_CR48","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1016\/j.exger.2006.06.040","volume":"41","author":"CT Murphy","year":"2006","unstructured":"Murphy, C. T. The search for DAF-16\/FOXO transcriptional targets: Approaches and discoveries. Exp. Gerontol. 41, 910\u2013921 (2006).","journal-title":"Exp. Gerontol."},{"key":"25984_CR49","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s10522-014-9527-y","volume":"16","author":"JMA Tullet","year":"2015","unstructured":"Tullet, J. M. A. DAF-16 target identification in C. elegans: past, present and future. Biogerontology 16, 221\u2013234 (2015).","journal-title":"Biogerontology"},{"key":"25984_CR50","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S0092-8674(00)00116-1","volume":"103","author":"RJ Davis","year":"2000","unstructured":"Davis, R. J. Signal Transduction by the JNK Group of MAP Kinases. Cell 103, 239\u2013252 (2000).","journal-title":"Cell"},{"key":"25984_CR51","doi-asserted-by":"publisher","unstructured":"Negi, H., Saikia, S. K. & Pandey, R. 3\u03b2-hydroxy-urs-12-en-28-oic acid modulates dietary restriction mediated longevity and ameliorates toxic protein aggregation in C. elegans. Journals Gerontol. Ser. A https:\/\/doi.org\/10.1093\/gerona\/glx118 (2017).","DOI":"10.1093\/gerona\/glx118"},{"key":"25984_CR52","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1002\/aoc.1026","volume":"20","author":"R Prabhakaran","year":"2006","unstructured":"Prabhakaran, R. et al. Preparation, spectral characterization, electro-chemistry, EXAFS, antibacterial and catalytic activity of new ruthenium (III) complexes containing ONS donor ligands with triphenylphosphine\/arsine. Appl. Organomet. Chem. 20, 203\u2013213 (2006).","journal-title":"Appl. Organomet. Chem."},{"key":"25984_CR53","doi-asserted-by":"publisher","first-page":"8620","DOI":"10.1039\/C7NJ01707C","volume":"41","author":"G Devagi","year":"2017","unstructured":"Devagi, G. et al. Morphological and in vitro evaluation of programmed cell death in MCF-7 cells by new organoruthenium(II) complexes. New J. Chem. 41, 8620\u20138636 (2017).","journal-title":"New J. Chem."},{"key":"25984_CR54","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1039\/C0MT00062K","volume":"3","author":"R Prabhakaran","year":"2011","unstructured":"Prabhakaran, R. et al. Synthesis, structure and biological evaluation of bis salicylaldehyde-4(N)-ethylthiosemicarbazone ruthenium(III) triphenylphosphine. Metallomics 3, 42\u201348 (2011).","journal-title":"Metallomics"},{"key":"25984_CR55","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/S0162-0134(01)00210-0","volume":"86","author":"J Garc\u00eda-Tojal","year":"2001","unstructured":"Garc\u00eda-Tojal, J. et al. Biological activity of complexes derived from thiophene-2-carbaldehyde thiosemicarbazone. Crystal structure of [Ni(C6H6N3S2)2]. J. Inorg. Biochem. 86, 627\u2013633 (2001).","journal-title":"J. Inorg. Biochem."},{"key":"25984_CR56","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1016\/j.poly.2009.02.042","volume":"28","author":"K Alomar","year":"2009","unstructured":"Alomar, K., Khan, M. A., Allain, M. & Bouet, G. Synthesis, crystal structure and characterization of 3-thiophene aldehyde thiosemicarbazone and its complexes with cobalt(II), nickel(II) and copper(II). Polyhedron 28, 1273\u20131280 (2009).","journal-title":"Polyhedron"},{"key":"25984_CR57","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.saa.2013.06.078","volume":"117","author":"AA Abou-Hussein","year":"2014","unstructured":"Abou-Hussein, A. A. & Linert, W. Synthesis, spectroscopic, coordination and biological activities of some organometallic complexes derived from thio-Schiff base ligands. Spectrochim. Acta - Part A Mol. Biomol. Spectrosc. 117, 763\u2013771 (2014).","journal-title":"Spectrochim. Acta - Part A Mol. Biomol. Spectrosc."},{"key":"25984_CR58","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1107\/S0108768102003890","volume":"58","author":"FH Allen","year":"2002","unstructured":"Allen, F. H. The Cambridge StructuralDatabase: A quarter of a million crystal structures and rising. Acta Crystallogr. Sect. B Struct. Sci. 58, 380\u2013388 (2002).","journal-title":"Acta Crystallogr. Sect. B Struct. Sci."},{"key":"25984_CR59","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1021\/om4010548","volume":"33","author":"MM Sheeba","year":"2014","unstructured":"Sheeba, M. M., Muthu Tamizh, M., Farrugia, L. J., Endo, A. & Karvembu, R. Chiral (\u03b76-p-cymene)ruthenium(II) complexes containing monodentate acylthiourea ligands for efficient asymmetric transfer hydrogenation of ketones. Organometallics 33, 540\u2013550 (2014).","journal-title":"Organometallics"},{"key":"25984_CR60","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/364337a0","volume":"364","author":"SL McIntire","year":"1993","unstructured":"McIntire, S. L., Jorgensen, E., Kaplan, J. & Horvitz, H. R. The GABAergic nervous system of Caenorhabditis elegans. Nature 364, 337\u2013341 (1993).","journal-title":"Nature"},{"key":"25984_CR61","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/29331","volume":"394","author":"N Ishii","year":"1998","unstructured":"Ishii, N. et al. A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature 394, 694\u2013697 (1998).","journal-title":"Nature"},{"key":"25984_CR62","doi-asserted-by":"publisher","DOI":"10.1038\/srep21611","volume":"6","author":"T Ogawa","year":"2016","unstructured":"Ogawa, T., Kodera, Y., Hirata, D., Blackwell, T. K. & Mizunuma, M. Natural thioallyl compounds increase oxidative stress resistance and lifespan in Caenorhabditis elegans by modulating SKN-1\/Nrf. Sci. Rep. 6, 21611 (2016).","journal-title":"Sci. Rep."},{"key":"25984_CR63","doi-asserted-by":"crossref","unstructured":"Lee, J., Kwon, G. & Lim, Y. H. Elucidating the Mechanism of Weissella-dependent Lifespan Extension in Caenorhabditis elegans. Sci. Rep. 5, (2015).","DOI":"10.1038\/srep17128"},{"key":"25984_CR64","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.cell.2014.10.039","volume":"159","author":"BK Kennedy","year":"2014","unstructured":"Kennedy, B. K. et al. Geroscience: Linking aging to chronic disease. Cell 159, 709\u2013713 (2014).","journal-title":"Cell"},{"key":"25984_CR65","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/j.exger.2012.05.005","volume":"47","author":"M Rodriguez","year":"2012","unstructured":"Rodriguez, M., Snoek, L. B., Riksen, J. A. G., Bevers, R. P. & Kammenga, J. E. Genetic variation for stress-response hormesis in C. elegans lifespan. Exp. Gerontol. 47, 581\u2013587 (2012).","journal-title":"Exp. Gerontol."},{"key":"25984_CR66","doi-asserted-by":"crossref","unstructured":"Hunt, P. R. et al. Extension of lifespan in C. elegans by naphthoquinones that act through stress hormesis mechanisms. PLoS One 6 (2011).","DOI":"10.1371\/journal.pone.0021922"},{"key":"25984_CR67","doi-asserted-by":"publisher","DOI":"10.1038\/srep41082","volume":"7","author":"C Zhang","year":"2017","unstructured":"Zhang, C. et al. Hormetic effect of panaxatriol saponins confers neuroprotection in PC12 cells and zebrafish through PI3K\/AKT\/mTOR and AMPK\/SIRT1\/FOXO3 pathways. Sci. Rep. 7, 41082 (2017).","journal-title":"Sci. Rep."},{"key":"25984_CR68","doi-asserted-by":"crossref","unstructured":"Fang, E. F. et al. Tomatidine enhances lifespan and healthspan in C. elegans through mitophagy induction via the SKN-1\/Nrf2 pathway. Sci. Rep. 7 (2017).","DOI":"10.1038\/srep46208"},{"key":"25984_CR69","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.cub.2005.12.038","volume":"16","author":"DR Valenzano","year":"2006","unstructured":"Valenzano, D. R. et al. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr. Biol. 16, 296\u2013300 (2006).","journal-title":"Curr. Biol."},{"key":"25984_CR70","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/j.1474-9726.2006.00192.x","volume":"5","author":"MA Wilson","year":"2006","unstructured":"Wilson, M. A. et al. Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans. Aging Cell 5, 59\u201368 (2006).","journal-title":"Aging Cell"},{"key":"25984_CR71","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.mad.2011.07.008","volume":"132","author":"VHC Liao","year":"2011","unstructured":"Liao, V. H. C. et al. Curcumin-mediated lifespan extension in Caenorhabditis elegans. Mech. Ageing Dev. 132, 480\u2013487 (2011).","journal-title":"Mech. Ageing Dev."},{"key":"25984_CR72","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/nature01789","volume":"424","author":"CT Murphy","year":"2003","unstructured":"Murphy, C. T. et al. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424, 277\u2013283 (2003).","journal-title":"Nature"},{"key":"25984_CR73","doi-asserted-by":"publisher","first-page":"4494","DOI":"10.1073\/pnas.0500749102","volume":"102","author":"SW Oh","year":"2005","unstructured":"Oh, S. W. et al. JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor\/DAF-16. Proc. Natl. Acad. Sci. USA 102, 4494\u20134499 (2005).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"25984_CR74","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1016\/j.exger.2006.09.004","volume":"41","author":"JR Cypser","year":"2006","unstructured":"Cypser, J. R., Tedesco, P. & Johnson, T. E. Hormesis and aging in Caenorhabditis elegans. Experimental Gerontology 41, 935\u2013939 (2006).","journal-title":"Experimental Gerontology"},{"key":"25984_CR75","doi-asserted-by":"publisher","first-page":"733","DOI":"10.18632\/aging.100367","volume":"3","author":"KI Zhou","year":"2011","unstructured":"Zhou, K. I., Pincus, Z. & Slack, F. J. Longevity and stress in Caenorhabditis elegans. Aging 3, 733\u2013753 (2011).","journal-title":"Aging"},{"key":"25984_CR76","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.jff.2016.08.012","volume":"26","author":"H Peixoto","year":"2016","unstructured":"Peixoto, H., Roxo, M., Krstin, S., Wang, X. & Wink, M. Anthocyanin-rich extract of Acai (Euterpe precatoria Mart.) mediates neuroprotective activities in Caenorhabditis elegans. J. Funct. Foods 26, 385\u2013393 (2016).","journal-title":"J. Funct. Foods"},{"key":"25984_CR77","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1016\/j.biopha.2017.09.096","volume":"95","author":"G Shanmugam","year":"2017","unstructured":"Shanmugam, G. et al. Diosgenin a phytosterol substitute for cholesterol, prolongs the lifespan and mitigates glucose toxicity via DAF-16\/FOXO and GST-4 in Caenorhabditis elegans. Biomed. Pharmacother. 95, 1693\u20131703 (2017).","journal-title":"Biomed. Pharmacother."},{"key":"25984_CR78","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/ng1723","volume":"38","author":"WO Seung","year":"2006","unstructured":"Seung, W. O. et al. Identification of direct DAF-16 targets controlling longevity, metabolism and diapause by chromatin immunoprecipitation. Nat. Genet. 38, 251\u2013257 (2006).","journal-title":"Nat. Genet."},{"key":"25984_CR79","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1038\/nm.4001","volume":"21","author":"S Kaushik","year":"2015","unstructured":"Kaushik, S. & Cuervo, A. M. Proteostasis and aging. Nat. Med. 21, 1406\u20131415 (2015).","journal-title":"Nat. Med."},{"key":"25984_CR80","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s13311-013-0192-7","volume":"10","author":"J Bieschke","year":"2013","unstructured":"Bieschke, J. Natural compounds may open new routes to treatment of amyloid diseases. Neurotherapeutics 10, 429\u2013439 (2013).","journal-title":"Neurotherapeutics"},{"key":"25984_CR81","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1371\/journal.pbio.1000450","volume":"8","author":"DC David","year":"2010","unstructured":"David, D. C. et al. Widespread protein aggregation as an inherent part of aging in C. elegans. PLoS Biol. 8, 47\u201348 (2010).","journal-title":"PLoS Biol."},{"key":"25984_CR82","doi-asserted-by":"publisher","first-page":"15022","DOI":"10.1038\/npjparkd.2015.22","volume":"1","author":"JF Cooper","year":"2015","unstructured":"Cooper, J. F. et al. Delaying aging is neuroprotective in Parkinson\u2019s disease: a genetic analysis in C. elegans models. npj Park. Dis. 1, 15022 (2015).","journal-title":"npj Park. Dis."},{"key":"25984_CR83","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.exger.2015.09.006","volume":"72","author":"K Hesp","year":"2015","unstructured":"Hesp, K., Smant, G. & Kammenga, J. E. Caenorhabditis elegans DAF-16\/FOXO transcription factor and its mammalian homologs associate with age-related disease. Experimental Gerontology 72, 1\u20137 (2015).","journal-title":"Experimental Gerontology"},{"key":"25984_CR84","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1042\/BJ20110621","volume":"441","author":"H Zhang","year":"2012","unstructured":"Zhang, H. et al. Inhibition of polyglutamine-mediated proteotoxicity by Astragalus membranaceus polysaccharide through the DAF-16\/FOXO transcription factor in Caenorhabditis elegans. Biochem. J. 441, 417\u201324 (2012).","journal-title":"Biochem. J."},{"key":"25984_CR85","first-page":"1223","volume":"29","author":"BS Furniss","year":"1989","unstructured":"Furniss, B. S., Hannaford, A. J., Smith, P. W. G. & Tatchell, A. R. Vogel\u2019s TEXTBOOK OF PRACTICAL ORGANIC CHEMISTRY 5th ED Revised - Brian S. Furniss. Journal of Polymer Science Part A: Polymer Chemistry 29, 1223\u20131223 (1989).","journal-title":"Journal of Polymer Science Part A: Polymer Chemistry"},{"key":"25984_CR86","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1107\/S0108767394005726","volume":"51","author":"RH Blessing","year":"1995","unstructured":"Blessing, R. H. An empirical correction for absorption anisotropy. Acta Crystallogr. Sect. A 51, 33\u201338 (1995).","journal-title":"Acta Crystallogr. Sect. A"},{"key":"25984_CR87","unstructured":"Sheldrick, G. M. SHELXTL Version 5.1, An Integrated System for Solving, Refining and Displaying Crystal Structures from Diffraction Data, Siemens Analytical X-ray Instruments, Madison, WI, (1990)."},{"key":"25984_CR88","unstructured":"Sheldrick, G. M. Shelxl-97, \u201cA Program for Crystal Structure Refinement Release\u201d, 97-2, Institut fur Anorganische Chemie der Universitat Gottingen, Tamman strasse 4, D-3400,Gottingen, Germany, (1998)."},{"key":"25984_CR89","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/j.ejmech.2014.05.075","volume":"82","author":"P Kalaivani","year":"2014","unstructured":"Kalaivani, P. et al. Biological evaluation of new nickel(II) metallates: Synthesis, DNA\/protein binding and mitochondrial mediated apoptosis in human lung cancer cells (A549) via ROS hypergeneration and depletion of cellular antioxidant pool. Eur. J. Med. Chem. 82, 584\u2013599 (2014).","journal-title":"Eur. J. Med. Chem."},{"key":"25984_CR90","doi-asserted-by":"publisher","first-page":"3735","DOI":"10.1021\/ic00318a024","volume":"28","author":"S Purohit","year":"1989","unstructured":"Purohit, S., Koley, A. P., Prasad, L. S., Manoharan, P. T. & Ghosh, S. Chemistry of molybdenum with hard-soft donor ligands. 2. molybdenum(VI), -(V), and -(IV) oxo complexes with tridentate dchiff base ligands. Inorg. Chem. 28, 3735\u20133742 (1989).","journal-title":"Inorg. Chem."},{"key":"25984_CR91","doi-asserted-by":"crossref","unstructured":"Bennett, M. A. & Smith, A. K. Arene ruthenium(II) complexes formed by dehydrogenation of cyclohexadienes with ruthenium(III) trichloride. Dalt. Trans. 233 (1974).","DOI":"10.1039\/dt9740000233"},{"key":"25984_CR92","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/genetics\/77.1.71","volume":"77","author":"S Brenner","year":"1974","unstructured":"Brenner, S. The genetics of Caenorhabditis elegans. Genetics 77, 71\u201394 (1974).","journal-title":"Genetics"},{"key":"25984_CR93","doi-asserted-by":"publisher","first-page":"B145","DOI":"10.1093\/geronj\/49.4.B145","volume":"49","author":"TJ Fabian","year":"1994","unstructured":"Fabian, T. J. & Johnson, T. E. Production of age-synchronous mass cultures of Caenorhabditis elegans. J. Gerontol. 49, B145\u2013B156 (1994).","journal-title":"J. Gerontol."},{"key":"25984_CR94","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.jep.2012.01.025","volume":"141","author":"X Yang","year":"2012","unstructured":"Yang, X. et al. The neuroprotective and lifespan-extension activities of Damnacanthus officinarum extracts in Caenorhabditis elegans. J. Ethnopharmacol. 141, 41\u201347 (2012).","journal-title":"J. Ethnopharmacol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25984-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25984-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25984-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T05:26:39Z","timestamp":1671600399000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25984-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,16]]},"references-count":94,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["25984"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-25984-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,16]]},"assertion":[{"value":"24 October 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 May 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 May 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"7688"}}