Title:Antitumor Effect of Zwitterions of Imidazolium Derived from L-methionine in BALB/c Mice with Lymphoma L5178Y
Volume: 17
Issue: 1
Author(s): Karen C. Vargas-Castro, Ana M. Puebla Pérez, Irma I. Rangel-Salas, Jorge I. Delgado-Saucedo, José B. Pelayo-Vázquez, Elvia Becerra-Martínez, Alejandro A. Peregrina-Lucano, Raul R. Quiñonez-Lopez, Gabriela J. Soltero-Reynoso and Sara A. Cortes-Llamas*
Affiliation:
- Departamento de Química, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Blvd. Marcelino García Barragán #1421, esq. Olímpica, C.P. 44430 Guadalajara, Jalisco,Mexico
Keywords:
Antitumor effect, lymphoma L5178Y, zwitterions of imidazoliuzwitterions of imidazolium, stereochemistry,
lysine, arginine.
Abstract: Background: In the therapy of cancer, several treatments have been designed using
nanomaterials, among which gold nanoparticles (AuNPs) have been featured as a promising antitumoral
agent. Our research group has developed the synthesis of gold nanoparticles L-AuNPs and
D-AuNPs stabilized with zwitterions of imidazolium (L-1 and D-1) derived from L-methionine
and D-methionine. Because the stabilizer agent is chiral, we observed through circular dichroism
that AuNPs also present chirality; such chirality as well as the fact that the stabilizing agent contains
fragments of methionine and imidazolium that are commonly involved in biological processes,
opens up the possibility that this system may have biological compatibility. Additionally, the
presence of methionine in the stabilizing agent opens the application of this system as a possible
antitumor agent because methionine is involved in methylation processes of molecules such as
DNA.
Objective: The aim of this research is the evaluation of the antitumor activity of gold nanoparticles
stabilized with zwitterions of imidazolium (L-AuNPs) derived from L-methionine in the model of
BALB/c mice with lymphoma L5178Y.
Methods: Taking as a parameter cell density, the evaluation of the inhibitory effect of L-AuNPs
was carried out with a series of in vivo tests in BALB/c type mice; three groups of five mice each
were formed (Groups 1, 2 and 3); all mice were i.p. inoculated with the lymphoblast murine
L5178Y. Group 1 consisted of mice without treatment. In the Groups 2 and 3 the mice were
treated with L-AuNPs at 0.3 mg/Kg on days 1, 7 and 14 by orally and intraperitonally respectively.
Results: These results show low antitumor activity of these gold nanoparticles (L-NPsAu) but interestingly,
the imidazolium stabilizing agent of gold nanoparticle (L-1) displayed promising antitumor
activity. On the other hand, the enantiomer of L-1, (D-1) as well as asymmetric imidazole
derivate from L-methionine (L-2), do not exhibit the same activity as L-1.
Conclusion: The imidazolium stabilizing agent (L-1) displayed promising antitumor activity.
Modifications in the structure of L-1 showed that, the stereochemistry (like D-1) and the presence
of methionine fragments (like L-2) are determinants in the antitumor activity of this compound.