title: Effect of [Cu(4,7-dimethyl-1,10-phenanthroline)(acetylacetonato)]NO3, Casiopeína III-Ea, on the activity of cytochrome P450.
abstract: Casiopeína III-Ea (Cas III-Ea(1)) is a copper complex with antiproliferative and antitumor activities, designed to act via alternative mechanisms of action different from Cisplatin. This compound has also been well characterized in preclinical test and pharmacokinetic analysis, being a good candidate for clinical phases. Since very little is known about the processes of biotransformation of therapeutic metal based drugs, this paper report the first approach to the study of the interaction between metal complex Cas III-Ea and cytochromes P450 with the aim to find out possible biotransformation pathways for this complexes and feasible drug-drug interactions. Results showed that Cas III-Ea is a strong irreversible competitive inhibitor of CYP1A1 (IC50 = 7.5 ± 1.0 μM; Ki = 240 nM). The magnitude of values indicate that it is necessary to be taken into account such effect when analyzing possible drug interactions with these new drugs in order to prevent adverse reactions derived from this inhibition.
authors.affiliation: Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México, Avenida Universidad 3000, DF CP 04510, Mexico.
authors.forename: Cristina
authors.initials: C
authors.lastname: Campero-Peredo
authors.affiliation: Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida Universidad 3000, DF CP 04510, Mexico. Electronic address: mebravo@unam.mx.
authors.forename: María Elena
authors.initials: ME
authors.lastname: Bravo-Gómez
authors.affiliation: Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Avenida Universidad 3000, DF CP04510, Mexico.
authors.forename: Sandra Luz
authors.initials: SL
authors.lastname: Hernández-Ojeda
authors.affiliation: Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Avenida Universidad 3000, DF CP04510, Mexico.
authors.forename: Sitlali Del Rosario
authors.initials: Sdel R
authors.lastname: Olguin-Reyes
authors.affiliation: Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Avenida Universidad 3000, DF CP04510, Mexico.
authors.forename: Javier J
authors.initials: JJ
authors.lastname: Espinosa-Aguirre
authors.affiliation: Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México, Avenida Universidad 3000, DF CP 04510, Mexico.
authors.forename: Lena
authors.initials: L
authors.lastname: Ruiz-Azuara
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D056831:Coordination Complexes / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010618:Phenanthrolines / Q000494:pharmacology*; D017208:Rats, Wistar
chemical_list: C586191:(Cu(4,7-dimethyl-1,10-phenanthroline)(acetylacetonato)(H2O))NO3; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D065607:Cytochrome P-450 Enzyme Inhibitors; D010618:Phenanthrolines; D003577:Cytochrome P-450 Enzyme System
keywords: Antitumor compounds; CYP1A1; Casiopeína III-Ea; Competitive inhibitors of cytochromes; Copper complexes; Metal-based drugs