ACS Medicinal Chemistry Letters
Letter
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
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S
Synthetic procedures, characterization of compounds, in
vitro kinetic procedure, X-ray crystallography, and
AUTHOR INFORMATION
Corresponding Author
ORCID
Author Contributions
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(14) Di Cesare Mannelli, L.; Micheli, L.; Carta, F.; Cozzi, A.;
Ghelardini, C.; Supuran, C. T. Carbonic anhydrase inhibition for the
management of cerebral ischemia: in vivo evaluation of sulfonamide
and coumarin inhibitors. J. Enzyme Inhib. Med. Chem. 2016, 31, 894−
899.
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
Notes
The authors declare no competing financial interest.
(15) De Simone, G.; Supuran, C. T. Antiobesity carbonic anhydrase
inhibitors. Curr. Top. Med. Chem. 2007, 7, 879.
ACKNOWLEDGMENTS
(16) Poulsen, S. A.; Wilkinson, B. L.; Innocenti, A.; Vullo, D.;
Supuran, C. T. Inhibition of human mitochondrial carbonic anhydrases
VA and VB with para-(4-phenyltriazole-1-yl)-benzenesulfonamide
derivatives. Bioorg. Med. Chem. Lett. 2008, 18, 4624.
(17) Supuran, C. T. Carbonic anhydrases: novel therapeutic
applications for inhibitors and activators. Nat. Rev. Drug Discovery
2008, 7, 168.
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We thank the Australian Synchrotron and the beamline
scientists for their help with data collection and thank OpenEye
Scientific Software for a license to the program Afitt. The C3
Crystallisation Centre (crystal.csiro.au) is acknowledged for all
crystallization experiments.
(18) Shah, G. N.; Rubbelke, T. S.; Hendin, J.; Nguyen, H.; Waheed,
A.; Shoemaker, J. D. Targeted mutagenesis of mitochondrial carbonic
anhydrases VA and VB implicates both enzymes in ammonia
detoxification and glucose metabolism. Proc. Natl. Acad. Sci. U. S. A.
2013, 110, 7423−7428.
(19) Deutsch, S. I.; Schwartz, B. L.; Rosse, R. B.; Mastropaolo, J.;
Marvel, C. L.; Drapalski, A. L. Adjuvant topiramate administration: a
pharmacologic strategy for addressing NMDA receptor hypofunction
in schizophrenia. Clin. Neuropharmacol. 2003, 26, 199−206.
(20) Nishimori, I.; Vullo, D.; Innocenti, A.; Scozzafava, A.;
Mastrolorenzo, A.; Supuran, C. T. Carbonic anhydrase inhibitors:
inhibition of the transmembrane isozyme XIV with sulfonamides.
Bioorg. Med. Chem. Lett. 2005, 17, 3828−3833.
(21) Angeli, A.; Tanini, D.; Peat, T. S.; Di Cesare Mannelli, L.;
Bartolucci, G.; Capperucci, A.; Ghelardini, C.; Supuran, C. T.; Carta, F.
Discovery of New Selenoureido Analogues of 4-(4-
Fluorophenylureido)benzenesulfonamide as Carbonic Anhydrase
Inhibitors. ACS Med. Chem. Lett. 2017, 8, 963−968.
(22) Tanini, D.; Panzella, L.; Amorati, R.; Capperucci, A.; Pizzo, E.;
Napolitano, A.; Menichetti, S.; d’Ischia, M. Resveratrol-based
benzoselenophenes with an enhanced antioxidant and chain breaking
capacity. Org. Biomol. Chem. 2015, 13, 5757−5764.
(23) Angeli, A.; Tanini, D.; Viglianisi, C.; Panzella, L.; Capperucci, A.;
Menichetti, S.; Supuran, C. T. Evaluation of selenide, diselenide and
selenoheterocycle derivatives as carbonic anhydrase I, II, IV, VII and
IX inhibitors. Bioorg. Med. Chem. 2017, 25, 2518−2523.
(24) Angeli, A.; Tanini, D.; Capperucci, A.; Supuran, C. T. Synthesis
of novel selenides bearing benzenesulfonamide moieties as carbonic
anhydrase I, II, IV, VII and IX inhibitors. ACS Med. Chem. Lett. 2017,
8, 1213−1217.
(25) Naganawa, A.; Matsui, T.; Ima, M.; Saito, T.; Murota, M.;
Aratani, Y.; Kijima, H.; Yamamoto, H.; Maruyama, T.; Ohuchida, S.;
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ABBREVIATIONS
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BBB, blood−brain barrier; CAs, carbonic anhydrases; ZBG,
zinc binding group; AAZ, acetazolamide; ZNS, zonisamide;
TPM, topiramate; RBE4, rat brain endothelial cell; GOx,
glucose oxidase; ETC, electron transfer chain
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