Introduction: Prostate cancer is one of the leading causes of death in men
worldwide. Its development occurs silently and slowly, with age being one of the risk
factors, as both incidence and mortality increase after the age of 50. The
development and progression of prostate cancer depends on androgen stimulation.
Cyproterone acetate (CPA), an antiandrogen steroid, is a drug that can block the
androgen receptor interaction and reduce serum testosterone through its
antigonadotropic action. Objective: The general objective was to identify potential
inhibitors with anti-prostate cancer activity by applying Bioinformatics techniques.
Material and Methods: The methodology adopted followed several steps such as:
selection of the pivot molecule (CPA) described in the literature with inhibitory action
on the androgen receptor interaction, and the information related to its structure and
crystallographic pose was obtained from the Protein Data Bank (PDB Code 2OZ7).
Virtual screening based on ligand and structure was carried out in 2 databases: Zinc
Drug Database and Princeton, through the ROCS and EON programs. Next, the
pharmacokinetic (Discovery Studio), toxicological (DEREK) and DL50 (Protox II)
properties were predicted, and the selected molecules were subjected to molecular
docking through the Dockthor online server, filtering the molecules that presented the
best affinity values. connection (G). Subsequently, synthetic viability, oral viability
and bioactivity studies were carried out. In addition to these steps, predictions of
biological activity (PASS), lipophilicity and water solubility were made (SwissADME).
Results and discussion: In the ROCS and EON stage, 500 molecules were
selected per database. They were subjected to pharmacokinetic (ADME),
toxicological and LD50 stages, leaving only 28 molecules for molecular docking. In the
molecular docking process, the molecules with the best binding affinity values (G)
were selected, which filtered out only 4 potential candidates. These 4 molecules went
through the predictions of molecular properties, bioactivity, biological activity,
lipophilicity and solubility in water, with only two molecules being hits: ZINC34176694
(G= -10.850 Kcal/mol; Pa=0.710) and ZINC03876158 (G= - 10.494 Kcal/mol;
Pa=0.993). Conclusions: The prediction results obtained for the molecules
ZINC34176694 and ZINC03876158 are satisfactory for being potential candidates as
inhibitors in the treatment of prostate cancer, especially the molecule ZINC03876158,
which showed excellent biological activity (Pa=0.993) for the androgen receptor.