Estudo computacional e planejamento de compostos derivados com ação inibitória potencial da proteína caseína quinase 2 (CK2)

Abstract

The protein casein kinase II (CK2) when overexpressed or when there is loss of function, has been related to neoplasms. Thus, the inhibition of CK2 presents itself as an interesting proposal for the discovery of new antitumor compounds. Derivatives of 2-aminothiazoles and derivatives of azonaphthalene are compounds with antitumor action with inhibitory activity on CK2. In order to obtain information and models that allow a greater and more detailed understanding of the antineoplastic activity of these compounds in this protein, this study was tool place out. The compounds were submitted to geometry optimization and conformational analysis using Spartan Sparta08 software for Windows. The 3D structure models of the CK2 protein were obtained from the Protein Database website (PDB ID: 3PE1, 5KU8, 4UB7 and 6TEI). The search for cavities was performed using the CavityPlus online server, where 1 druggable cavity was obtained for 3PE1, 3 for 5KU8, 1 for 4UB7 and 2 for 6TEI. Previous studies on activity prediction and search for similarity, using the Self Ensemble Approach (SEA) online platform, demonstrated that only 2-aminothiazoles derivatives showed significant results in relation to azonaphthalenes, with potential interaction with CK2 and with an index of similarity of 0.3 to each other. The pharmacophore LBDD model was obtained by the Pharmagist software, which was loaded on the ZincPharmer server, allowing the realization of virtual screening, where a compound was chosen because it presents the 2- aminothiazole group and an acid function. For the model obtained by the pharmacophare SBDD, the Pharmit software was used, as well as the virtual screening of this step, where five compounds were obtained from digital banks of small molecules. The compounds obtained by virtual screening showed no toxic effect and three of them showed a prediction of positive biological activity for CK2. The docking molecular study was performed using iGemdock 2.1 software with the 3D structures of the CK2 protein, 2-aminothiazole derivatives and the compound obtained by virtual screening with pharmacophare LBDD. These interactions occur with the main amino acid residues of the active active, according to recent literature. It is suggested that the 3D models of the CK2 protein used in this work may be competent for the planning and development of new bioactive compounds that show active inhibition from 2-aminothiazole derivatives that have promising antineoplastic activity.