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Design and synthesis of biphenyl and biphenyl ether inhibitors of sulfatases
journal contribution
posted on 2023-06-09, 00:43 authored by Tristan Reuillon, Sari F Alhasan, Gary S Beale, Annalisa Bertoli, Alfie Brennan, Celine Cano, Helen L Reeves, David R Newell, Bernard T Golding, Duncan C Miller, Roger J GriffinInhibitors of sulfatase-2 are putative anticancer agents, but the discovery of potent small molecules targeting this enzyme has proved challenging. Based on molecular modelling, two series of sulfatase-2 inhibitors have been developed with biphenyl and biphenyl ether scaffolds judiciously substituted with sulfamate, carboxylate and other polar groups (e.g. amino). Inhibition of aryl sulfatase A and B was also determined. The biphenyl ether derivatives were less selective for sulfatase-2 over aryl sulfatase B than the biphenyl series. All biphenyl ether derivatives inhibited aryl sulfatase A, whereas only amino derivatives inhibited aryl sulfatase B significantly. In the biphenyl series few derivatives exhibited activity against aryl sulfatase B. The trichloroethylsulfamate group was identified as a new pharmacophore enabling potent inhibition of all of the sulfatases studied.
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Publication status
- Published
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- Published version
Journal
Chemical ScienceISSN
2041-6520Publisher
Royal Society of ChemistryExternal DOI
Issue
4Volume
7Page range
2821-2826Department affiliated with
- Chemistry Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2016-03-31First Compliant Deposit (FCD) Date
2016-03-31Usage metrics
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