Comparative Study of Aromatase Enzyme Inhibition by Synthetic and Natural Ligand: Molecular Modeling and Conceptual DFT Investigation

Background: Inhibition of aromatase enzyme presents the key in Breast cancer treatment actually an important number of synthetics and natural inhibitors of this enzyme were studied. However, steroidal synthetic inhibitors were identified as the most efficient ones, indeed, the most commercialized treatment of breast cancer is steroidal. On the other hand, natural inhibitors have also provided good activities via the aromatase enzyme (Gingerol, Capsaïcine, Rhizome). Methods: In this work, we present a comparative, theoretical study of aromatase enzyme inhibitors by steroidal and natural inhibitors by means of molecular docking and conceptual DFT (Density functional theory) approaches. Theoretical calculations were done using the MOE programme for molecular docking and Gaussian 09 package for DFT calculation using B3lyp/6-31g* level of theory. Results: The DFT study was done for the best natural and synthetic inhibitors (deducted from the docking best scores for Lig5 and Lig 9, and lowest score for Lig ref). The relative global reactivity of these systems is rationalized by means of the global softness index. The present study shows that the Docking trends of the relative activities of these inhibitors are correlated with their predicted softness indexes. Conclusion: The obtained Docking and DFT results lead to the same conclusion and predict that exemestane is the best inhibitor which is synthetic and natural.