Rozan H Mehder, Elena de la Torre-Rubio, Isabel de la Cueva-Alique, Ciaran O’Malley, A. Pérez-Redondo, Lourdes Gude, Eva Royo, Luca Ronconi
{"title":"作为治疗和成像肿瘤的潜在金属otheranostic制剂的荧光维生素 B12-铂(II)衍生物","authors":"Rozan H Mehder, Elena de la Torre-Rubio, Isabel de la Cueva-Alique, Ciaran O’Malley, A. Pérez-Redondo, Lourdes Gude, Eva Royo, Luca Ronconi","doi":"10.3390/inorganics12030091","DOIUrl":null,"url":null,"abstract":"Vitamin B12 (cyanocobalamin) is an essential nutrient with very low bioavailability. Compared with normal cells, tumor cells show an increased demand for vitamin B12 to support their abnormal proliferation, which is a feature that can be exploited for the tumor-specific delivery of therapeutic and/or diagnostic agents by functionalizing vitamin B12 with suitable metallodrugs and/or luminescent probes. In this context, we report on the design of fluorescent vitamin B12–metal conjugates of the type [FLUO–B12–{M}] in which cyanocobalamin is functionalized at the 5′-site of the ribose unit with a fluorophore (FLUO: rhodamine 6G), whereas the Co(III)–cyano moiety is N-coordinated to a metal-based anticancer scaffold ({M}: Pt(II) substrate bearing enantiopure phenylamino-oxime ligands derived from R- or S-limonene). Two novel fluorescent cyanocobalamin–platinum(II) derivatives and their corresponding non-fluorescent counterparts were successfully generated and fully characterized, including the evaluation of their lipophilicity and luminescent properties. Although they exhibit low antiproliferative activity (IC50 = 40–70 μM), both fluorescent vitamin B12–platinum(II) conjugates showed an enhanced capability to inhibit cell viability compared with the inactive metal precursors and the non-fluorescent vitamin B12–platinum(II) analogues, confirming the beneficial effect of functionalization with the rhodamine 6G scaffold not only for imaging purposes but also with the aim of improving their biological activity.","PeriodicalId":507601,"journal":{"name":"Inorganics","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Fluorescent Vitamin B12–Platinum(II) Derivatives as Potential Metallotheranostic Agents for the Treatment and Imaging of Tumors\",\"authors\":\"Rozan H Mehder, Elena de la Torre-Rubio, Isabel de la Cueva-Alique, Ciaran O’Malley, A. Pérez-Redondo, Lourdes Gude, Eva Royo, Luca Ronconi\",\"doi\":\"10.3390/inorganics12030091\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Vitamin B12 (cyanocobalamin) is an essential nutrient with very low bioavailability. Compared with normal cells, tumor cells show an increased demand for vitamin B12 to support their abnormal proliferation, which is a feature that can be exploited for the tumor-specific delivery of therapeutic and/or diagnostic agents by functionalizing vitamin B12 with suitable metallodrugs and/or luminescent probes. In this context, we report on the design of fluorescent vitamin B12–metal conjugates of the type [FLUO–B12–{M}] in which cyanocobalamin is functionalized at the 5′-site of the ribose unit with a fluorophore (FLUO: rhodamine 6G), whereas the Co(III)–cyano moiety is N-coordinated to a metal-based anticancer scaffold ({M}: Pt(II) substrate bearing enantiopure phenylamino-oxime ligands derived from R- or S-limonene). Two novel fluorescent cyanocobalamin–platinum(II) derivatives and their corresponding non-fluorescent counterparts were successfully generated and fully characterized, including the evaluation of their lipophilicity and luminescent properties. Although they exhibit low antiproliferative activity (IC50 = 40–70 μM), both fluorescent vitamin B12–platinum(II) conjugates showed an enhanced capability to inhibit cell viability compared with the inactive metal precursors and the non-fluorescent vitamin B12–platinum(II) analogues, confirming the beneficial effect of functionalization with the rhodamine 6G scaffold not only for imaging purposes but also with the aim of improving their biological activity.\",\"PeriodicalId\":507601,\"journal\":{\"name\":\"Inorganics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-03-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Inorganics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/inorganics12030091\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Inorganics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/inorganics12030091","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Fluorescent Vitamin B12–Platinum(II) Derivatives as Potential Metallotheranostic Agents for the Treatment and Imaging of Tumors
Vitamin B12 (cyanocobalamin) is an essential nutrient with very low bioavailability. Compared with normal cells, tumor cells show an increased demand for vitamin B12 to support their abnormal proliferation, which is a feature that can be exploited for the tumor-specific delivery of therapeutic and/or diagnostic agents by functionalizing vitamin B12 with suitable metallodrugs and/or luminescent probes. In this context, we report on the design of fluorescent vitamin B12–metal conjugates of the type [FLUO–B12–{M}] in which cyanocobalamin is functionalized at the 5′-site of the ribose unit with a fluorophore (FLUO: rhodamine 6G), whereas the Co(III)–cyano moiety is N-coordinated to a metal-based anticancer scaffold ({M}: Pt(II) substrate bearing enantiopure phenylamino-oxime ligands derived from R- or S-limonene). Two novel fluorescent cyanocobalamin–platinum(II) derivatives and their corresponding non-fluorescent counterparts were successfully generated and fully characterized, including the evaluation of their lipophilicity and luminescent properties. Although they exhibit low antiproliferative activity (IC50 = 40–70 μM), both fluorescent vitamin B12–platinum(II) conjugates showed an enhanced capability to inhibit cell viability compared with the inactive metal precursors and the non-fluorescent vitamin B12–platinum(II) analogues, confirming the beneficial effect of functionalization with the rhodamine 6G scaffold not only for imaging purposes but also with the aim of improving their biological activity.