Design and synthesis of biphenyl and biphenyl ether inhibitors of sulfatases

Reuillon, Tristan, Alhasan, Sari F, Beale, Gary S, Bertoli, Annalisa, Brennan, Alfie, Cano, Celine, Reeves, Helen L, Newell, David R, Golding, Bernard T, Miller, Duncan C and Griffin, Roger J (2016) Design and synthesis of biphenyl and biphenyl ether inhibitors of sulfatases. Chemical Science, 7 (4). pp. 2821-2826. ISSN 2041-6520

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Abstract

Inhibitors 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.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry
Depositing User: Tristan Reuillon
Date Deposited: 31 Mar 2016 14:41
Last Modified: 08 Mar 2017 05:25
URI: http://sro.sussex.ac.uk/id/eprint/60206

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