Isomeric Effect on the Pharmacokinetic Behavior of Anticancer Cu-II Mixed Chelate Complexes: Experimental and Theoretical Approach
Por:
Carlos Garcia-Ramos, Juan, Vertiz-Serrano, Guadalupe, Macias-Rosales, Lucia, Galindo-Murillo, Rodrigo, Toledano-Magana, Yanis, Pablo Bernal, Juan, Cortes-Guzman, Fernando, Ruiz-Azuara, Lena
Publicada:
27 mar 2017
Categoría:
Inorganic chemistry
Resumen:
We present herein the results of a pharmacokinetic (PK) study of Cu-II
mixed-chelate coordination compound CasIII-La
{[Cu(5,6-dimethyl-1,10-phenanthroline)(acetylacetonate)( H2O)] NO3,
which belongs to the antineoplastic family of compounds known as
Casiopenas. The main interest in this molecule lies in the big
difference in its lethal dose and PK parameters in Wistar rats compared
with its structural isomer CasIII-Ea
{[Cu(4,7-dimethyl-1,10-phenanthroline)(acetylacetonate)(H2O)]NO3.
For instance, the half-lives of these compounds are 9.6 +/- 1.15 and 48
+/- 4.6 h for CasIII-La and CasIII-Ea, respectively. The differences in
the half- lives have been attributed to their different capacities to
cross cellular membranes. Molecular dynamics studies of a fraction of a
cell membrane and Casiopenas were developed to identify the possible
intermolecular interactions responsible for the retention of the
compound inside the cellular membrane. Also, quantum theory of
atoms-in-molecules studies was developed to determine the capacity of
the hydrogen atoms of methyl groups to participate in intermolecular
interactions. In addition, peripheral human blood lymphocyte and
macrophage samples were used to determine the cross-membrane effect on
cytotoxicity.
Filiaciones:
Univ Nacl Autonoma Mexico, Inst Quim, Dept Fisicoquim, Ave Univ 3000,Ciudad Univ, Mexico City 04510, DF, Mexico
Univ Nacl Autonoma Mexico, Fac Quim, Dept Quim Inorgan & Nucl, Ave Univ 3000,Ciudad Univ, Mexico City 04510, DF, Mexico
Univ Utah, Dept Med Chem, LS Skaggs Pharm Inst, Salt Lake City, UT 84112 USA
Univ Nacl Autonoma Mexico, Ctr Geociencias, Campus UNAM Juriquilla,Cd Univ, Mexico City 04510, DF, Mexico
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