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Title: Design and synthesis of thiourea compounds that inhibit transmembrane anchored carbonic anhydrases
Contributor(s): Moeker, Janina (author); Teruya, Kanae (author); Rossit, Sabine (author); Wilkinson, Brendan  (author)orcid ; Lopez, Marie (author); Bornaghi, Laurent F (author); Innocenti, Alessio (author); Supuran, Claudiu T (author); Poulsen, Sally-Ann (author)
Publication Date: 2012
DOI: 10.1016/j.bmc.2012.01.052
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Abstract: A library of 32 novel glycoconjugate thiourea-bridged benzene sulfonamides have been synthesized from the reaction of glycosyl isothiocyanates with a panel of simple benzene sulfonamides comprising either a free amine or hydrazide. All compounds were investigated for their ability to inhibit the enzymatic activity of five human carbonic anhydrase (hCA) isozymes: hCA I, II and membrane-associated isozymes IX, XII and XIV. A physicochemical feature of the free sugar thioureido glycoconjugates was high water solubility (>20 mg/mL), as well many of these compounds exhibited a desirable potency and CA isozyme selectivity profile. From this library several inhibitors displayed excellent potency-selectivity profiles for transmembrane anchored CAs over off-target CA I and II. These molecules provide potential dual-acting candidates for the development of inhibitors that target the extracellular CAs (IX, XII and XIV)-either directly as free sugars (membrane impermeable) or indirectly as acetylated prodrugs, becoming free sugars upon esterase hydrolysis.
Publication Type: Journal Article
Source of Publication: Bioorganic & Medicinal Chemistry, 20(7), p. 2392-2404
Publisher: Pergamon Press
Place of Publication: United Kingdom
ISSN: 0968-0896
Field of Research (FOR): 030401 Biologically Active Molecules
030503 Organic Chemical Synthesis
030405 Molecular Medicine
Socio-Economic Outcome Codes: 920102 Cancer and Related Disorders
970106 Expanding Knowledge in the Biological Sciences
970103 Expanding Knowledge in the Chemical Sciences
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
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