Design, synthesis and biological activity of selective hCAs inhibitors based on 2-(benzylsulfinyl)benzoic acid scaffold

Giulia Rotondi, Paolo Guglielmi, Simone Carradori, Daniela Secci, Celeste De Monte, Barbara De Filippis, Cristina Maccallini, Rosa Amoroso, Roberto Cirilli, Atilla Akdemir, Andrea Angeli, Claudiu T Supuran

Research output: Contribution to journalArticlepeer-review

Abstract

A large library of derivatives based on the scaffold of 2-(benzylsulfinyl)benzoic acid were synthesised and tested as atypical inhibitors against four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). The exploration of the chemical space around the main functional groups led to the discovery of selective hCA IX inhibitors in the micromolar/nanomolar range, thus establishing robust structure-activity relationships within this versatile scaffold. HPLC separation of some selected chiral compounds and biological evaluation of the corresponding enantiomers was performed along with molecular modelling studies on the most active derivatives.

Original languageEnglish
Pages (from-to)1400-1413
Number of pages14
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume34
Issue number1
DOIs
Publication statusPublished - Dec 2019

Keywords

  • Benzoic Acid/chemistry
  • Carbonic Anhydrase Inhibitors/chemical synthesis
  • Carbonic Anhydrases/drug effects
  • Catalytic Domain
  • Chromatography, High Pressure Liquid
  • Drug Design
  • Humans
  • Isoenzymes/drug effects
  • Molecular Docking Simulation
  • Stereoisomerism
  • Structure-Activity Relationship

Fingerprint

Dive into the research topics of 'Design, synthesis and biological activity of selective hCAs inhibitors based on 2-(benzylsulfinyl)benzoic acid scaffold'. Together they form a unique fingerprint.

Cite this