Kinetic and X-ray crystallographic investigations on carbonic anhydrase isoforms I, II, IX and XII of a thioureido analog of SLC-0111

Bioorganic & Medicinal Chemistry
Carrie L LomelinoClaudiu T Supuran

Abstract

SLC-0111 (4-(4-fluorophenylureido)-benzenesulfonamide) is the first carbonic anhydrase (CA, EC 4.2.1.1) IX inhibitor to reach phase I clinical trials as an antitumor/antimetastatic agent. Here we report a kinetic and X-ray crystallographic study of a congener of SLC-0111 which incorporates a thioureido instead of ureido linker between the two aromatic rings as inhibitor of four physiologically relevant CA isoforms. Similar to SLC-0111, the thioureido derivative was a weak hCA I and II inhibitor and a potent one against hCA IX and XII. X-ray crystallography of its adduct with hCA II and comparison of the structure with that of other five hCA II-sulfonamide adducts belonging to the SLC-0111 series, afforded us to understand the particular inhibition profile of the new sulfonamide. Similar to SLC-0111, the thioureido sulfonamide primarily interacted with the hydrophobic side of the hCA II active site, with the tail participating in van der Waals interactions with Phe131 and Pro202, in addition to the coordination of the deprotonated sulfonamide to the active site metal ion. On the contrary, the tail of other sulfonamides belonging to the SLC-0111 series (2-isopropyl-phenyl; 3-nitrophenyl) were orientated towards the hydrophilic ha...Continue Reading

References

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Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jan 3, 2008·Nature Reviews. Drug Discovery·Claudiu T Supuran
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Dec 2, 2015·Journal of Enzyme Inhibition and Medicinal Chemistry·Claudiu T Supuran

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Citations

Jun 15, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wagdy M EldehnaHatem A Abdel-Aziz
Jun 30, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Claudiu T Supuran, Clemente Capasso
Jul 9, 2016·Expert Opinion on Therapeutic Patents·Carrie Lomelino, Robert McKenna
Jul 21, 2016·Biochemistry·Brian P MahonRobert McKenna
Oct 27, 2016·Expert Opinion on Drug Discovery·Claudiu T Supuran
Mar 30, 2017·Bioorganic & Medicinal Chemistry·Fabrizio CartaClaudiu T Supuran
Jul 26, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Rosa PerfettoClemente Capasso
Apr 9, 2020·Journal of Biomolecular Structure & Dynamics·Shafi MahmudMd Abu Saleh
Aug 19, 2020·Expert Opinion on Therapeutic Patents·Claudiu T Supuran, Clemente Capasso
Sep 15, 2020·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Carlotta ZoppiLuigi Messori
May 1, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Benoit MétayerSébastien Thibaudeau
Oct 18, 2020·Metabolites·Andrea AngeliClaudiu T Supuran
Dec 29, 2020·Journal of Experimental Pharmacology·Claudiu T Supuran
Jan 13, 2021·International Journal of Molecular Sciences·Viviana De LucaClemente Capasso
Jul 25, 2019·Bioorganic Chemistry·Immo SerbianRené Csuk
May 22, 2020·ACS Medicinal Chemistry Letters·Francesca MancusoRosaria Gitto
Feb 23, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Alessio NocentiniClaudiu T Supuran
Apr 6, 2021·Frontiers in Microbiology·Cristina CampestreClemente Capasso
May 4, 2021·Chembiochem : a European Journal of Chemical Biology·Michael KuglerBohumír Grüner
Sep 7, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Alessio NocentiniClemente Capasso

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