Chemical reactivity of the domain of union of the hormonal receptors with the tamoxifen and its different metabolites

According with the World Health Organization, breast cancer it represents 16 % of female cancers worldwide. Cancer can be called estrogen-receptor-positive or progesterone-receptor-positive, it depends of the signals received... [ view full abstract ]

According with the World Health Organization, breast cancer it represents 16 % of female cancers worldwide. Cancer can be called estrogen-receptor-positive or progesterone-receptor-positive, it depends of the signals received by the cancer cells from estrogen or progesterone to promote their growth. The study of the hormone receptor is important to define the right treatment.

One of the treatments used for hormone receptors is tamoxifen (TAM) known as a selective estrogen receptor modulator (SERMs) [1, 2]. It is used for the treatment of hormone receptors that express breast cancer [3]. This drug is metabolized in the liver producing three different metabolites: 4-hydroxy-TAM (4OHTAM), N-dismethyl-TAM (NDTAM) and 4-hydroxy-N-dismethyl-TAM also known as endoxifene (END) [4, 5]. Both the TAM molecule and its three metabolites are considered SERMs, due to their ability to bind to hormone receptors.

The present work reports the characterization and molecular docking of TAM and its metabolites with the macromolecules estrogen receptor (ER) and progesterone receptor (PR) to obtain an active site of the hormone receptors. A charge transfer analysis was also performed using the amino acids of the active site of the hormone receptor. Also, the chemical reactivity of the amino acids of the active sites of each ligand (TAM, 4OHTAM, NDTAM and END) was determined. The results were obtained within the framework of the Density Functional Theory (DFT) with the theory level M06 / 6-31G (d) and the continuous model of solvation CPCM using water with solvent. The use of the molecular docking technique allowed us to find that TAM has a highest more effectiveness in estrogen receptors than in progesterone receptors. The highest charge transfer is in the Leu 346-Thr 347 residue with -0.1000 in the ER and -0.076 in the residue Leu 718-Asn 719 in the PR.