{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T09:32:17Z","timestamp":1772184737072,"version":"3.50.1"},"reference-count":57,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T00:00:00Z","timestamp":1628380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/50011\/2020 and UIDP\/50011\/2020; Centro-01-0145-FEDER-029956; UIDB\/00070\/2020; UIDB\/50006\/2020;SFRH\/BD\/ 111576\/2015"],"award-info":[{"award-number":["UIDB\/50011\/2020 and UIDP\/50011\/2020; Centro-01-0145-FEDER-029956; UIDB\/00070\/2020; UIDB\/50006\/2020;SFRH\/BD\/ 111576\/2015"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Portuguese National NMR Network (PTNMR)","award":["Project N\u00ba 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL, and the FCT through PIDDAC)"],"award-info":[{"award-number":["Project N\u00ba 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL, and the FCT through PIDDAC)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This paper reports the first metabolomics study of the impact of new chelates Pt2Spm and Pd2Spm (Spm = Spermine) on human osteosarcoma cellular metabolism, compared to the conventional platinum drugs cisplatin and oxaliplatin, in order to investigate the effects of different metal centers and ligands. Nuclear Magnetic Resonance metabolomics was used to identify meaningful metabolite variations in polar cell extracts collected during exposure to each of the four chelates. Cisplatin and oxaliplatin induced similar metabolic fingerprints of changing metabolite levels (affecting many amino acids, organic acids, nucleotides, choline compounds and other compounds), thus suggesting similar mechanisms of action. For these platinum drugs, a consistent uptake of amino acids is noted, along with an increase in nucleotides and derivatives, namely involved in glycosylation pathways. The Spm chelates elicit a markedly distinct metabolic signature, where inverse features are observed particularly for amino acids and nucleotides. Furthermore, Pd2Spm prompts a weaker response from osteosarcoma cells as compared to its platinum analogue, which is interesting as the palladium chelate exhibits higher cytotoxicity. Putative suggestions are discussed as to the affected cellular pathways and the origins of the distinct responses. This work demonstrates the value of untargeted metabolomics in measuring the response of cancer cells to either conventional or potential new drugs, seeking further understanding (or possible markers) of drug performance at the molecular level.<\/jats:p>","DOI":"10.3390\/molecules26164805","type":"journal-article","created":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T21:35:40Z","timestamp":1628458540000},"page":"4805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Response of Osteosarcoma Cell Metabolism to Platinum and Palladium Chelates as Potential New Drugs"],"prefix":"10.3390","volume":"26","author":[{"given":"Ana S.","family":"Martins","sequence":"first","affiliation":[{"name":"CICECO\u2014Aveiro Institute of Materials (CICECO\/UA), Department of Chemistry, University of Aveiro, Campus Universit\u00e1rio de Santiago, 3810-193 Aveiro, Portugal"},{"name":"Unidade de I&D Qu\u00edmica-F\u00edsica Molecular, Department of Chemistry, University of Coimbra, Rua Larga, 300-535 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1280-3321","authenticated-orcid":false,"given":"Ana L. M.","family":"Batista de Carvalho","sequence":"additional","affiliation":[{"name":"Unidade de I&D Qu\u00edmica-F\u00edsica Molecular, Department of Chemistry, University of Coimbra, Rua Larga, 300-535 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8391-0055","authenticated-orcid":false,"given":"Maria P. M.","family":"Marques","sequence":"additional","affiliation":[{"name":"Unidade de I&D Qu\u00edmica-F\u00edsica Molecular, Department of Chemistry, University of Coimbra, Rua Larga, 300-535 Coimbra, Portugal"},{"name":"Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Cal\u00e7ada Martim de Freitas, 3000-456 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3766-4364","authenticated-orcid":false,"given":"Ana M.","family":"Gil","sequence":"additional","affiliation":[{"name":"CICECO\u2014Aveiro Institute of Materials (CICECO\/UA), Department of Chemistry, University of Aveiro, Campus Universit\u00e1rio de Santiago, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer Statistics 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA-Cancer J. 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