Interaction energies between two antiandrogenic and one androgenic agonist receptor in the presence of a T877A mutation in prostate cancer: a quantum chemistry analysis

Abstract

Prostate cancer is the most prevalent malignancy in men, and one of the top causes of cancer death. Great advances have been presented regarding the treatment and understanding of the biology of this disease although, unfortunately, the available therapies do not demonstrate the desired efficacy. Moreover, it is already known that androgen receptor (AR) activation is critical for the growth of prostate cancer at all points of the disease, and therefore therapies targeting this receptor are widely used. In this context, the action of antiandrogen agents has been clinically used for the treatment of the disease. However, it does not present the desired response regarding the blockade of cancer cells, especially in scenarios where mutations occur. Taking into account the above remarks, we intend in this work to use quantum chemistry methods based on Density Functional Theory (DFT) in the molecular fragmentation with conjugate caps (MFCC) approach to evaluate the interaction energies involving two antiandrogenic and one androgenic agonist compounds, in a complex with the AR carrying a T877A mutation. The results demonstrate similarities and distinctions in the interactions between different ligands and the T877A-AR mutation by investigating the major residues involved in the interactions of these biological complex systems. The computational method used here emerges as an elegant and efficient alternative for the development of drugs that may present a better response in prostate cancer therapy.