The comparison of the effect of different inhibitors on aromatase enzyme effective in the breast cancer by molecular docking method

Background: Aromatase is an enzyme that plays an important role in the development of estrogen-positive breast cancer. Estrogens are essential in human and mainly in women because of their role in sexual development and reproduction. Adverse effects of some aromatase inhibitors increase the need to discover new inhibitors with higher selectivity, lower toxicity and improved potency. In this study, the binding state of all three generations of aromatase inhibitors to the molecular structure of this protein using molecular docking method has been studied. Materials and methods: In general, the inhibitors based on steroid scaffolds (formestane and exemestane) have higher binding energy than azole scaffolds (fadrozole, anastrozole, letrozole), which may be due to their high structural strength. Results: Among all the considered structures studied, exemestane had the highest (negative) binding energy as well as the lowest inhibitory constant. The free energy of binding and the inhibitory constants was -8.77 kcal mol-1 and 373.32 nM respectively, which means that aromatase activity will be inhibited at the low concentrations of this anti-cancer drug. Conclusion: The knowledge gained from this study will have important implications regarding for pharmaceutical design.