Unconventional amino acids in medicinal chemistry: First report on taurine merged within carbonic anhydrase inhibitors

Bioorg Chem. 2020 Oct;103:104236. doi: 10.1016/j.bioorg.2020.104236. Epub 2020 Aug 26.

Abstract

This study reports the design, synthesis of a series of taurine containing benzenesulfonamide derivatives which were all screened in vitro against the physiological relevant human (h) expressed Carbonic Anhydrase (CA; EC 4.2.1.1) I, II, IX, XII isozymes. Compound 2, 5, 11-16 displayed superior inhibitory activities against the tumor associated hCA IX over the reference drug Acetazolamide (AAZ). Both hCA IX and XII isoforms were selectively inhibited only by compound 3, whereas the chloro-containing compound 12 was showed as the most selective and effective inhibitor profile for the CA IX isoforms. To the best of our knowledge the data reported herein are the first of this kind and introduce in the literature new compounds worth for future development within the Medicinal Chemistry field.

Keywords: Benzenesulfonamide; Carbonic Anhydrase Inhibitors (CAIs); Structure-Activity Relationship (SAR); Taurine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrases / chemistry
  • Drug Design
  • Enzyme Assays
  • Humans
  • Isoenzymes / chemistry
  • Kinetics
  • Molecular Structure
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Taurine / analogs & derivatives*
  • Taurine / chemical synthesis

Substances

  • Carbonic Anhydrase Inhibitors
  • Isoenzymes
  • Sulfonamides
  • Taurine
  • Carbonic Anhydrases