2026-05-30T13:53:42Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/68252026-02-06T12:50:50Zcom_10259_4363com_10259_5086com_10259_2604com_10259_4365col_10259_4364col_10259_4366

Rubio Antolin, Ana Rosa González, Rocío Busto Vázquez, Natalia Vaquero Gutiérrez, Mónica Iglesias, Ana L. Jalón Sotés, Félix Ángel Espino Ordóñez, Gustavo Rodríguez, Ana M. García Ruiz, Begoña Manzano, Blanca R. . 2022-09-01T08:24:11Z 2022-09-01T08:24:11Z 2021-09 1999-4923 http://hdl.handle.net/10259/6825 10.3390/pharmaceutics13101540 1999-4923 An important challenge in the field of anticancer chemotherapy is the search for new species to overcome the resistance of standard drugs. An interesting approach is to link bioactive ligands to metal fragments. In this work, we have synthesized a set of p-cymene-Ru or cyclopentadienyl-M (M = Rh, Ir) complexes with four chrysin-derived pro-ligands with different -OR substituents at position 7 of ring A. The introduction of a piperidine ring on chrysin led to the highly cytotoxic pro-ligand HL4 and its metal complexes L4-M (SW480 and A549 cell lines, cytotoxic order: L4-Ir > L4-Ru ≈ L4-Rh). HL4 and its complexes induce apoptosis and can overcome cis-platinum resistance. However, HL4 turns out to be more cytotoxic in healthy than in tumor cells in contrast to its metal complexes which displayed higher selectivity than cisplatin towards cancer cells. All L4-M complexes interact with double stranded DNA. Nonetheless, the influence of the metal is clear because only complex L4-Ir causes DNA cleavage, through the generation of highly reactive oxygen species (1O2 ). This result supports the hypothesis of a potential dual mechanism consisting of two different chemical pathways: DNA binding and ROS generation. This behavior provides this complex with a great effectivity in terms of cytotoxicity Spanish Ministerio de Ciencia, Innovación y UniversidadesFEDER (RTI2018-100709-B-C21 and RTI2018-102040-B-100), Junta de Comunidades de CastillaLa Mancha-FEDER (JCCM) (grant SBPLY/19/180501/000260), Junta de Castilla y León-FEDER (BU087G19 and BU305P18), “la Caixa” Foundation (LCF/PR/PR12/11070003), as well as by UCLMFEDER (grants 2019-GRIN-27183 and 2019-GRIN-27209). application/pdf eng MDPI Pharmaceutics. 2021, V. 13, n. 10, 1540 https://doi.org/10.3390/pharmaceutics13101540 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-100709-B-C21/ES/NUEVOS METALOFARMACOS DISEÑADOS PARA INCREMENTAR LA SELECTIVIDAD EN TRATAMIENTOS CONTRA EL CANCER. USO DE FOTOTERAPIA Y VEHICULIZACION CON LIGANDOS DIRIGIDOS A TUMORES info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-102040-B-I00/ES/PROPIEDADES ANTIMICROBIANAS DE NUEVOS COMPLEJOS ORGANOMETALICOS info:eu-repo/grantAgreement/JCCM//SBPLY%2F19%2F180501%2F000260 info:eu-repo/grantAgreement/Junta de Castilla y León//BU087G19 info:eu-repo/grantAgreement/Junta de Castilla y León//BU305P18 info:eu-repo/grantAgreement/Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona//LCF%2FPR%2FPR12%2F11070003 info:eu-repo/grantAgreement/UCLM//2019-GRIN-27183 info:eu-repo/grantAgreement/UCLM//2019-GRIN-27209 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Chrysin ligands Iridium Ruthenium Rhodium Cancer Metallodrugs Piperidine Half-sandwich Bioquímica Química inorgánica Química física Biochemistry Chemistry, Inorganic Chemistry, Physical and theoretical Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Pharmaceutics 13 10 1540