Norma Flores-Holguin
Centro de Investigación en Materiales Avanzados,S.C.
Materials Science PhD Norma Rosario Flores-Holguín is a researcher for the Advanced Materials Research Center in Chihuahua, México. She has more than 38 papers in Scientific Journals and 40 International Congress contributions. She is manager of the Molecular Modelling and Computational Chemistry Laboratory, where is carried out projects of design of nanocarriers for drugs with theoretical methods.Currently her research group has theoretically designed a drug-nanodiamond carrier for Tamoxifen with the aim of avoid the side effects and deliver tamoxifen to cells with improved efficiency. This protocol is now at In vitro phase in the bionanotechnology lab in her Institution.
Introduction The estrogen receptors (ER) have allowed offering a better prognosis to patients with breast cancer. The most common treatment is Tamoxifen (TAM), a Selective Estrogen Receptor Modulator (SERM), which can inhibit... [ view full abstract ]
Introduction
The estrogen receptors (ER) have allowed offering a better prognosis to patients with breast cancer. The most common treatment is Tamoxifen (TAM), a Selective Estrogen Receptor Modulator (SERM), which can inhibit the estrogen effects in the breast cancer neoplastic cells without altering the beneficial effects it has on bone, cardiovascular and nervous system [1]. However, even though TAM has good results, it also has side effects such as blood clots and endometrial cancer.
For this reason a study of the theoretical reactivity parameters of two cell-surface receptors, arginine-glycine-aspartic acid tripeptide (RGD) that is present in the glycoprotein fibronectine and Aspargine-Glycine-Arganine tripeptide (NGR) found in the aminopeptidase, was developed trying to find their interaction with TAM drug.
Methodology
The computational characterization of the peptides RGD and NGR, and the complex ND-TAM/RGD, ND-TAM/NGR, and ND-TAM complex was made using the Conceptual Density Functional Theory, DFT [2] with M06 functional [3] and 6-31G (d) basis set [4]. The reactivity parameters as ionization potential, electron affinity and chemical hardness were calculated. The cross reactivity was done and the frontier orbitals were obtained for all the studied systems.
Results and Discussion
According with electronic density distribution, the ND-TAM complex inactivates the drug on its surface. This does not permit to bind it with the cell-surface receptors in healthy cells. Nevertheless, the difference in pH of cancer cells will allow the binding in the active site of the receptor. The analysis of the frontier molecular orbitals confirm the inactivation of TAM when it is carried by the nanodiamond. It can be observed in Figure 1. Also, the cross-reactivity indicated that TAM reacts with greater facility in presence of RGD than NGR.
Keywords: breast cancer, Tamoxifen, Estrogen Receptor, DFT
[1] F. Cammarata-Scalisi1, M. Balza, A. Arenas de, M.M. Sotolongo, F. Stock, J.L. Valderrama-Landaeta, Revista Médica de la Extensión Portuguesa, 2 (2008)
[2]. P. Hohenberg, W. Kohn, Physical Review, 136 (1964) B864-B871.
[3] Y. Zhao, D. Truhlar, Theoretical Chemistry Accounts, 120 (2008) 215-241.
[4] V.A. Rassolov, M.A. Ratner, J.A. Pople, P.C. Redfern, L.A. Curtiss, Journal of Computational Chemistry, 22 (2001) 976-984.
