Abstract CT408: Phase I study of one mixed chelates copper(II) compound, Casiopeína CasIIIia with antitumor activity and its mechanism of action
2014; American Association for Cancer Research; Volume: 74; Issue: 19_Supplement Linguagem: Inglês
10.1158/1538-7445.am2014-ct408
ISSN1538-7445
AutoresLena Ruiz‐Azuara, Gérard Bastian, María Elena Bravo‐Gómez, Roberto Carlos Cañas, Marcos Flores-Ãlamo, Inés Fuentes, Carmen Mejía, Juan Carlos García‐Ramos, Alberto Serrano,
Tópico(s)Metal complexes synthesis and properties
ResumoAbstract Metal complexes have gained a growing interest as pharmaceuticals for their use as diagnostic agents or as chemotherapeutic drugs[1]. In our group some efforts have been done in the development of anticancer agents employing essential metals such as the family of copper (II) compounds known as Casiopeínas®, with a general formula [Cu (N-N) (X-Y) H2O] NO3 where N-N is a diimine (phen or bipy) and X-Y is a bidentate ligand (acac, salal, aminoacidate, peptide, benzimidazol). These compounds have shown cytostatic, cytotoxic and antineoplastic activity in vitro and in vivo[2]. Also albumin/Casiopeinas interaction is discussed. Among those one have selected that is CasIII-ia as the most adequate to go into clinical trial Phase I. Although the mechanism of action is still not completely elucidated, experimental evidence suggests the interaction of coordination compounds with DNA (nuclear or mitochondrial) and their components and the generation of reactive oxygen species (ROS) as the main action pathways. Induction of apoptosis has been proved to be the main death tumoral cell pathway. DNA cleavage capacity, compared with the 4, 4´-diimine analogs, then is suggested an intercalation process as the first step for the DNA damage. Also calculations have been done in order to modeling the interaction between Casiopeínas and DNA [3, 4]. The clinical protocol phase I of the dimethyl bpy derivative with acac Cas IIIia is presented and the selection criteria of the drug. [1] S. H. van Rijt, P. J. Sadler, Drug Discov. Today, 14 (2009) 1089-1097. [2] L. Ruiz-Azuara, M.E. Bravo-Gómez, Curr. Med. Chem., 17 (2010) 3606-3615. [3] R. Galindo-Murillo, J. Hernández-Lima, M. González-Rendón, F. Cortés-Guzmán, L. Ruíz-Azuara, R. Moreno-Esparza Phys. Chem. Chem. Phys., 13 (2011) 14511-14516. [4] R. Galindo-Murillo, L. Ruiz-Azuara, R. Moreno-Esparza, F. Cortés-Guzmán Phys. Chem. Chem. Phys., 14 (2012) 15539-15546. Citation Format: Lena Ruiz-Azuara, Gerard Bastian, Maria Elena Bravo-Gómez, Roberto Carlos Cañas, Marcos Flores-Alamo, Ines Fuentes, Carmen Mejia, Juan Carlos García-Ramos, Alberto Serrano. Phase I study of one mixed chelates copper(II) compound, Casiopeína CasIIIia with antitumor activity and its mechanism of action. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT408. doi:10.1158/1538-7445.AM2014-CT408
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