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Synthesis and biological evaluation of N ‐acylated tyramine sulfamates containing C–F bonds as steroid sulfatase inhibitors
Author(s) -
Daśko Mateusz,
Rachon Janusz,
Masłyk Maciej,
Kubiński Konrad,
Demkowicz Sebastian
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12931
Subject(s) - steroid sulfatase , steroid , sulfation , chemistry , tyramine , coumarin , sulfatase , stereochemistry , biological activity , enzyme , docking (animal) , biochemistry , hormone , in vitro , organic chemistry , medicine , nursing
Steroid sulfatase ( STS ) is responsible for the hydrolysis of biologically inactive sulfated steroids into their active un‐sulfated forms and promotes the growth of various hormone‐dependent cancers (e.g., breast cancer). Therefore, the STS enzyme is a promising therapeutic target for the treatment of steroid‐sensitive cancers. Herein, we report the synthesis and biological evaluation of sulfamate analogs as potential STS inhibitors based on N ‐acylated tyramines that contain C–F bonds. The inhibitory effects of the analogs were tested using STS isolated from human placenta. Of the analogs tested, 4‐(2‐perfluoroundecanoylaminoethyl)‐phenyl sulfamate, 5r , demonstrated the greatest inhibitory effect, with an IC 50 value of 2.18 μ m ( IC 50 value of 2.13 μ m for coumarin‐7‐ O ‐sulfamate was used as a reference). These findings were supported by the results our computational analyses performed using molecular docking techniques.