Azobenzene-based inhibitors of human carbonic anhydrase II

Leander Simon Runtsch, David Michael Barber, Peter Mayer, Michael Groll, Dirk Trauner, Johannes Broichhagen

Research output: Contribution to journalArticle

Abstract

Aryl sulfonamides are a widely used drug class for the inhibition of carbonic anhydrases. In the context of our program of photochromic pharmacophores we were interested in the exploration of azobenzene-containing sulfonamides to block the catalytic activity of human carbonic anhydrase II (hCAII). Herein, we report the synthesis and in vitro evaluation of a small library of nine photochromic sulfonamides towards hCAII. All molecules are azobenzene-4-sulfonamides, which are substituted by different functional groups in the 4'-position and were characterized by X-ray crystallography. We aimed to investigate the influence of electron-donating or electron-withdrawing substituents on the inhibitory constant Ki. With the aid of an hCAII crystal structure bound to one of the synthesized azobenzenes, we found that the electronic structure does not strongly affect inhibition. Taken together, all compounds are strong blockers of hCAII with Ki = 25-65 nM that are potentially photochromic and thus combine studies from chemical synthesis, crystallography and enzyme kinetics.

Original languageEnglish (US)
Pages (from-to)1129-1135
Number of pages7
JournalBeilstein Journal of Organic Chemistry
Volume11
DOIs
StatePublished - Jul 7 2015

Fingerprint

Carbonic Anhydrase II
Sulfonamides
Enzyme kinetics
Carbonic Anhydrases
Crystallography
Electrons
X ray crystallography
Functional groups
Electronic structure
Catalyst activity
Crystal structure
Molecules
azobenzene
Pharmaceutical Preparations

Keywords

  • Azobenzene chemistry
  • Enzyme inhibitors
  • Human carbonic anhydrase ii
  • Sulfonamide
  • X-ray crystallography

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Runtsch, L. S., Barber, D. M., Mayer, P., Groll, M., Trauner, D., & Broichhagen, J. (2015). Azobenzene-based inhibitors of human carbonic anhydrase II. Beilstein Journal of Organic Chemistry, 11, 1129-1135. https://doi.org/10.3762/bjoc.11.127

Azobenzene-based inhibitors of human carbonic anhydrase II. / Runtsch, Leander Simon; Barber, David Michael; Mayer, Peter; Groll, Michael; Trauner, Dirk; Broichhagen, Johannes.

In: Beilstein Journal of Organic Chemistry, Vol. 11, 07.07.2015, p. 1129-1135.

Research output: Contribution to journalArticle

Runtsch, LS, Barber, DM, Mayer, P, Groll, M, Trauner, D & Broichhagen, J 2015, 'Azobenzene-based inhibitors of human carbonic anhydrase II', Beilstein Journal of Organic Chemistry, vol. 11, pp. 1129-1135. https://doi.org/10.3762/bjoc.11.127
Runtsch LS, Barber DM, Mayer P, Groll M, Trauner D, Broichhagen J. Azobenzene-based inhibitors of human carbonic anhydrase II. Beilstein Journal of Organic Chemistry. 2015 Jul 7;11:1129-1135. https://doi.org/10.3762/bjoc.11.127
Runtsch, Leander Simon ; Barber, David Michael ; Mayer, Peter ; Groll, Michael ; Trauner, Dirk ; Broichhagen, Johannes. / Azobenzene-based inhibitors of human carbonic anhydrase II. In: Beilstein Journal of Organic Chemistry. 2015 ; Vol. 11. pp. 1129-1135.
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