Structure Based Design of Potential Inhibitors of Steroid Sulfatase

Abstract

The enzyme steroid sulfatase (STS) activity is high in breast tumors and elevated levels of STS mRNA expression have been associated with a poor prog- nosis. Potent STS irreversible inhibitors have been developed, paving the way to use this new type of therapy for breast cancer. Synthetic small molecules belonging to a focused library of inhibitors of tumor cell growth already obtained and new molecules planned to be reversible inhibitors of STS were docked into STS using the program AutoDock 4. To guide the docking process of the select ligands through the lattice volume that divides the receptor's area of interest, a full set of grid maps was built using the program AutoGrid. Some of the new designed small molecules showed calculated binding affinity for STS presenting ΔG values in a range of -11.15 to -13.07 kcal.mol-1. The synthesis of the most promising STS inhibitors, based on these results, is in progress. 1