Synthesis of rhodamine B-benzenesulfonamide conjugates and their inhibitory activity against human α- and bacterial/fungal β-carbonic anhydrases

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5210-3. doi: 10.1016/j.bmcl.2011.07.045. Epub 2011 Jul 21.

Abstract

A series of fluorescent sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors were obtained by attaching rhodamine B moieties to the scaffold of benzenesulfonamides. The new compounds have been investigated for the inhibition of 12 human α-CA isoforms (hCA I-hCA XIV), three bacterial and one fungal β-class enzymes from the pathogens Mycobacterium tuberculosis and Candida albicans. All types of inhibitory activities have been detected, with several compounds showing low nanomolar inhibition against the transmembrane isoforms hCA IX, XII (cancer-associated) and XIV. The β-CAs were inhibited in the micromolar range by these compounds which may have applications for the imaging of hypoxic tumors or bacteria due to their fluorescent moieties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzenesulfonamides
  • Candida albicans / enzymology*
  • Carbonic Anhydrase Inhibitors / chemical synthesis*
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / metabolism*
  • Humans
  • Molecular Structure
  • Mycobacterium tuberculosis / enzymology*
  • Rhodamines / chemistry*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Sulfonamides / chemistry*

Substances

  • Carbonic Anhydrase Inhibitors
  • Rhodamines
  • Sulfonamides
  • Carbonic Anhydrases
  • rhodamine B