New potent STS inhibitors based on fluorinated 4-(1-phenyl-1H-[1,2,3]triazol-4-yl)-phenyl sulfamates

Abstract

A series of fluorinated analogs based on the frameworks of 4-(1-phenyl-1H-[1,2,3]triazol-4-yl)-phenyl sulfamates have been synthesized as steroid sulfatase (STS) inhibitors. The design of chemical structures of new potential STS inhibitors was supported by molecular docking techniques to identify potential interactions between inhibitors and amino acid residues located in the STS active site. The STS inhibitory potency was evaluated on STS isolated from human placenta. We found that compounds substituted with fluorine atom at the meta position demonstrated the highest inhibitory effects in enzymatic STS assay. The most active analog 12e – inhibited STS enzyme with the IC₅₀ value of 36 nM.

Graphical Abstract

Keywords:

• Triazoles
• steroid sulfatase
• breast cancer
• STS inhibitors
• sulfamates

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We gratefully acknowledge the National Science Centre (Poland) for financial support (PRELUDIUM grant no. 2015/19/N/NZ7/00938 and ETIUDA fellowship no. 2017/24/T/NZ7/00271). Furthermore, we gratefully acknowledge the Foundation for Polish Science (FNP) for financial support in the form of the fellowship START for one of the coauthors.