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://srodev.sussex.ac.uk/id/eprint/60206

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