D.S. Zolotykh, E.T. Oganesian, I.P. Kodonidi, S.H. Mucueva

Development of new NSAIDs inhibiting cyclooxygenase 2 (COX2) is the actual way of investigation in medicinal chemistry. Authors in this work demonstrate inhibiting COX2 property of quinazolin-4-ones with the help of molecular modeling methods. Derivatives of above mentioned heterocyclic system were used as the basis of the test sample. During the analysis of the last one complementary centers (amino acid residues) of known COX2 inhibitors were established. This fact makes possible to calculate interaction energies between ligand and enzyme. The same way was used for predicted structures. The prediction model was created in two stages. During first stage molecular docking of test sample structures and predictive structures was provided. The resultant docking energy was used as one of molecular descriptors. On the second stage values of other descriptors were calculated with the help of Mold 2 free software. The prediction model was based on linear and square regression. During validation of the model R2 and Q2 parameters were evaluated. The result of the model was the leader compound. This fact was proved by the result of pharmacological studies. The leader compound demonstrated higher biological activity in comparison with comparators.