title: Ruthenium-containing P450 inhibitors for dual enzyme inhibition and DNA damage.
abstract: Cytochrome P450s are key players in drug metabolism, and overexpression in tumors is associated with significant resistance to many medicinal agents. Consequently, inhibition of P450s could serve as a strategy to restore drug efficacy. However, the widespread expression of P450s throughout the human body and the critical roles they play in various biosynthetic pathways motivates the development of P450 inhibitors capable of controlled local administration. Ruthenium complexes containing P450 inhibitors as ligands were synthesized in order to develop pro-drugs that can be triggered to release the inhibitors in a spatially and temporally controlled fashion. Upon light activation the compounds release ligands that directly bind and inhibit P450 enzymes, while the ruthenium center is able to directly damage DNA.
authors.affiliation: Departamento de Química Inorgánica and Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, and Institute for Bio-Health Research of Murcia (IMIB-Arrixaca), E-30071 Murcia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Zamora
authors.affiliation: Department of Chemistry, University of Kentucky, 505 Rose Street, Lexington, KY 40506, USA. ec.glazer@uky.edu.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Denning
authors.affiliation: Department of Chemistry, University of Kentucky, 505 Rose Street, Lexington, KY 40506, USA. ec.glazer@uky.edu.
authors.forename: David K
authors.initials: DK
authors.lastname: Heidary
authors.affiliation: Department of Chemistry, University of Kentucky, 505 Rose Street, Lexington, KY 40506, USA. ec.glazer@uky.edu.
authors.forename: Erin
authors.initials: E
authors.lastname: Wachter
authors.affiliation: Department of Chemistry, University of Kentucky, 505 Rose Street, Lexington, KY 40506, USA. ec.glazer@uky.edu.
authors.forename: Leona A
authors.initials: LA
authors.lastname: Nease
authors.affiliation: Departamento de Química Inorgánica and Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, and Institute for Bio-Health Research of Murcia (IMIB-Arrixaca), E-30071 Murcia, Spain.
authors.forename: José
authors.identifier: http://orcid.org/0000-0002-0834-337X
authors.initials: J
authors.lastname: Ruiz
authors.affiliation: Department of Chemistry, University of Kentucky, 505 Rose Street, Lexington, KY 40506, USA. ec.glazer@uky.edu.
authors.forename: Edith C
authors.identifier: http://orcid.org/0000-0002-0190-7742
authors.initials: EC
authors.lastname: Glazer
mesh_terms: D001554:Benzene / Q000737:chemistry; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D007093:Imidazoles / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D012428:Ruthenium / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; C029899:imidazole; D012428:Ruthenium; D003577:Cytochrome P-450 Enzyme System; D001554:Benzene