In silico and in vitro Estimation of Structure and Biological Affinity of 1,3-Oxazoles: Fragment-to-fragment Approach

Background: The fragment-to-fragment approach for the estimation of the biological affinity of the pharmacophores with biologically active molecules has been proposed. It is the next step in the elaboration of molecular docking and using the quantum-chemical methods for the complex modeling of pharmacophores with biomolecule fragments. Methods: The parameter phi 0 was used to estimate the contribution of re-electron interactions in biological affinity. It is directly related to the position of the frontier levels and reflects the donor-acceptor properties of the pharmacophores and stabilization energy of the [Pharm:BioM] complex. Results: By using quantum-chemical calculations, it was found that the stacking interaction of oxazoles with phenylalanine is 7-11 kcal/mol, while the energy of hydrogen bonding of oxazoles with the amino group of lysine is 5-9 kcal/mol. The fragment-to-fragment approach can be applied for the investigation of the dependence of biological affinity on the electronic structure of pharmacophores. Conclusion: The founded quantum-chemical regularities are confirmed with the structure-activity relationships of substituted oxazoles.