title: Highly potent extranuclear-targeted luminescent iridium(iii) antitumor agents containing benzimidazole-based ligands with a handle for functionalization.
abstract: A series of 6 substitutionally inert and luminescent iridium(iii) antitumor agents of the type [Ir(C∧N)2(N∧N)][PF6] containing a benzimidazole N∧N ligand with an ester group as a handle for further functionalization has been prepared. They exhibit IC50values in the high nanomolar range in some ovarian and breast cancer cell lines (approximately 100× more cytotoxic than cisplatin (CDDP) in MDA-MB-231) and are located in the actin cortex predominantly as shown by confocal luminescence microscopy. This discovery could open the door to a new large family of drug bioconjugates with diverse and simultaneous functions.
authors.affiliation: Departamento de Química Inorgánica and Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, and Biomedical Research Institute of Murcia (IMIB-Arrixaca), E-30071 Murcia, Spain. jruiz@um.es.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Yellol
authors.affiliation: Departamento de Química Inorgánica and Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, and Biomedical Research Institute of Murcia (IMIB-Arrixaca), E-30071 Murcia, Spain. jruiz@um.es.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Pérez
authors.affiliation: Departamento de Química Inorgánica and Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, and Biomedical Research Institute of Murcia (IMIB-Arrixaca), E-30071 Murcia, Spain. jruiz@um.es.
authors.forename: Gorakh
authors.initials: G
authors.lastname: Yellol
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i. Kralovopolska 135, 612 65 Brno, Czech Republic. brabec@ibp.cz and Department of Biophysics, Faculty of Science, Palacky University, Slechtitelu 27, 783 71 Olomouc, Czech Republic.
authors.forename: Juraj
authors.initials: J
authors.lastname: Zajac
authors.affiliation: Departamento de Química Inorgánica and Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, and Biomedical Research Institute of Murcia (IMIB-Arrixaca), E-30071 Murcia, Spain. jruiz@um.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Donaire
authors.affiliation: Departamento de Química Inorgánica and Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, and Biomedical Research Institute of Murcia (IMIB-Arrixaca), E-30071 Murcia, Spain. jruiz@um.es.
authors.forename: Gloria
authors.initials: G
authors.lastname: Vigueras
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i. Kralovopolska 135, 612 65 Brno, Czech Republic. brabec@ibp.cz.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Novohradsky
authors.affiliation: Institut für Anorganische Chemie und Strukturchemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.
authors.forename: Christoph
authors.identifier: http://orcid.org/0000-0002-6288-9605
authors.initials: C
authors.lastname: Janiak
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i. Kralovopolska 135, 612 65 Brno, Czech Republic. brabec@ibp.cz and Department of Biophysics, Faculty of Science, Palacky University, Slechtitelu 27, 783 71 Olomouc, Czech Republic.
authors.forename: Viktor
authors.initials: V
authors.lastname: Brabec
authors.affiliation: Departamento de Química Inorgánica and Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, and Biomedical Research Institute of Murcia (IMIB-Arrixaca), E-30071 Murcia, Spain. jruiz@um.es.
authors.forename: José
authors.identifier: http://orcid.org/0000-0002-0834-337X
authors.initials: J
authors.lastname: Ruiz
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007495:Iridium / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D049449:Luminescence; D018613:Microscopy, Confocal; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D008024:Ligands; D009942:Organometallic Compounds; D007495:Iridium; C031000:benzimidazole