Polycystic ovary syndrome (PCOS) is the most common cause of infertility without ovulation. Aromatase inhibitors were first proposed as new ovulation-inducing drugs in anovulatory women with an inadequate response to clomiphene. Letrozole is an aromatase inhibitor used as an ovulation inducer in infertile women due to PCOS. However, there is no definitive treatment for women with PCOS and the treatments are mostly symptomatic. In this study, we intend to introduce alternative drugs to letrozole using the library of FDA-approved drugs and evaluate the interaction of these drugs with the aromatase receptor. For this aim, molecular docking was performed to identify interactions of FDA-approved drugs with essential residues in the active site of the aromatase receptor. 1614 FDA-approved drugs were docked with aromatase receptor using AutoDock Vina. Molecular dynamics (MD) simulation study was also performed for 100 ns to verify the stability of the drug-receptor complexes. MMPBSA analysis evaluate the binding energy of selected complexes. Finally, acetaminophen, alendronate, ascorbic acid, aspirin, glutamine, hydralazine, mesalazine and pseudoephedrine drugs showed the best results in interaction with aromatase receptor based on computational studies. These drugs can be introduced as an alternative to letrozole for treating PCOS.Communicated by Ramaswamy H. Sarma.
Keywords: FDA-approved; PCOS; aromatase; molecular docking; molecular dynamics (MD) simulation.