SILVA, Rafaela Bezerra da.
Résumé:
The rational design of drugs has been widely used for drug development more effective in the treatment of various diseases, including cancer. This term used and hair diseases caused set cluttered cell growth, tissues and organs to invade que own body and can spread throughout the body, process called metastasis. Between how several research aimed at new training drugs for tumor treatment is molecular target therapy, which is based on the use of drugs that inactivate a particular cancer cell protein. Molecular biology has identified several proteins related to cancer, among these are Midkina (MK) and Glutathione S-Transferase Pi class (GSTP1), associated with the multiplication capacity and resistance of tumors, respectively. The development of a specific inhibitor that present both for GSTP1 and MK as to enable a free damage to normal cells treatment and better quality of life for cancer patients. This study aimed to design a molecule capable of inhibiting the biological activity of MK and GST in that condition. Using resources like search website Protein Data Bank (PDB) for obtaining the studied three-dimensional structures, the Basic Local Alignment Search Tool (BLAST) for alignment and analysis of protein sequences, the Hex 8.0 software for the realization of molecular docking test and WinCoot 0.7.1 to identify the hydrophobic intermolecular interactions and hydrogen generated in the analyzed complexes. For the development of the molecule were used as the template inhibitors 6-(7-nitro-2, 1, 3-benzoxadiazol-4-Ylthio) Hexanol (NBDHEX) and 5-propylthio-1H-benzimidazol-2-yl) carbamate (Albendazol). The developed inhibitor (RBT15) was designed using previously deposited in PDB structures and trimmed to meet the topological characteristics of the receivers. The tests showed that the analyzed RBT15 binder is energetically more favorable and demonstrated interaction with a larger number of residues of interest than the other two analyzed inhibitors. The data suggest that the developed structure might be a potential inhibitor of GSTP1 and MK proteins. Since, therefore, a promising molecule for the development of more efficient and less invasive drugs for the treatment of cancer.
