Cancer is a leading cause of death worldwide,accounting for nearly 10 million deaths in 2020.Palladium complexes can be used as anticancer and pharmacological agents as a promising alternative to overcome the disadvan...Cancer is a leading cause of death worldwide,accounting for nearly 10 million deaths in 2020.Palladium complexes can be used as anticancer and pharmacological agents as a promising alternative to overcome the disadvantages of platinum drugs,controlling the speciation in solution and limiting toxicity.In this study,two novel complexes were developed and their speciation in solution was deeply investigated,demonstrating their stability in solution together with their behavior versus nucleic acid models and serum proteins via thermodynamic studies.Furthermore,both complexes were demonstrated to be efficient and more specific than the benchmark cisplatin drug because of their lower toxicity to healthy cells.展开更多
The design of trans-platinum(II)complexes marked a significant turning point in the development of unconventional anticancer metallodrugs.Compared to cisplatin,these complexes induce distinctly different cellular resp...The design of trans-platinum(II)complexes marked a significant turning point in the development of unconventional anticancer metallodrugs.Compared to cisplatin,these complexes induce distinctly different cellular responses and are often active against cisplatin-resistant cell lines.In this study,we synthesized and fully characterized two new Pt(II)complexes,introducing one acetate(-OCOCH_(3))ligand(X)into the trans-PtXX’axis,where X’is either acetate or chlorido.We evaluated their cytotoxicity across a panel of malignant(Capan-1,B16,MCF7,HCT-116,CT26 and P31)and non-malignant(HaCaT,HUVEC,BEC,and MCF10A)cell lines,finding that the complex with only one acetate trans to a chlorido group is more active and selective than the complex with two acetates(X=X’).Furthermore,the two complexes differ from cisplatin in their cellular uptake route as well as mode of action by inducing cancer cell death via non-DNA-associated mechanisms.展开更多
基金part of the work of CA18202 of the NECTAR Network for Equilibria and Chemical Thermodynamics Advanced Research,supported by the COST(European Cooperation in Science and Technology)the Spanish MINECO grant PID2019-106220RB100 and MetDrugs Network RED2018-102471T for research discussion+3 种基金CIRCMSB(Consorzio Inter-Universitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici)and CISUP(Centro per la Integrazione della Strumentazione dell’Universitàdi Pisa)the“Comunidad de Madrid”and European Regional Development Fund-FEDER 2014-2020-OE REACT-UE 1 for financial support to the VIRMOF-CM project associated with R&D projects in response to COVID-19,the Multifunctional Metallodrugs in Diagnosis and Therapy Network(MICIU,RED2018-102471-T)the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie grant agreement No 897678(NeuroMOF)the Spanish Ramon y Cajal Programme(grant agreement no.2014 to 16823).
文摘Cancer is a leading cause of death worldwide,accounting for nearly 10 million deaths in 2020.Palladium complexes can be used as anticancer and pharmacological agents as a promising alternative to overcome the disadvantages of platinum drugs,controlling the speciation in solution and limiting toxicity.In this study,two novel complexes were developed and their speciation in solution was deeply investigated,demonstrating their stability in solution together with their behavior versus nucleic acid models and serum proteins via thermodynamic studies.Furthermore,both complexes were demonstrated to be efficient and more specific than the benchmark cisplatin drug because of their lower toxicity to healthy cells.
基金Dr.A.Álvarez-Valdés for their early contribution to this work.This research was funded by CTQ2015-68779-R and PID2019-106220RB-I00granted by Agencia Estatal de Investigación from the Spanish Ministerio de Ciencia e Innovación and Ministerio de Economía y Competitividad+1 种基金All biological studies were funded by the Austrian Research Service(FWF)project FG3 and P37111Theresa Mendrina was funded via the Obermann-Mahlke Stiftung.
文摘The design of trans-platinum(II)complexes marked a significant turning point in the development of unconventional anticancer metallodrugs.Compared to cisplatin,these complexes induce distinctly different cellular responses and are often active against cisplatin-resistant cell lines.In this study,we synthesized and fully characterized two new Pt(II)complexes,introducing one acetate(-OCOCH_(3))ligand(X)into the trans-PtXX’axis,where X’is either acetate or chlorido.We evaluated their cytotoxicity across a panel of malignant(Capan-1,B16,MCF7,HCT-116,CT26 and P31)and non-malignant(HaCaT,HUVEC,BEC,and MCF10A)cell lines,finding that the complex with only one acetate trans to a chlorido group is more active and selective than the complex with two acetates(X=X’).Furthermore,the two complexes differ from cisplatin in their cellular uptake route as well as mode of action by inducing cancer cell death via non-DNA-associated mechanisms.
