Synthesis of a new series of quinoline/pyridine indole-3-sulfonamide hybrids as selective carbonic anhydrase IX inhibitors

Bioorg Med Chem Lett. 2022 Aug 15:70:128809. doi: 10.1016/j.bmcl.2022.128809. Epub 2022 May 21.

Abstract

In this manuscript, design, rational, synthesisand carbonic anhydrases (CAs) inhibitory profile of the quinoline/pyridine linked indole-3-sulfonamide derivatives were reported. The library of 29newly quinoline/pyridine indole-3-sulfonamide derivatives have been generated and examined against the panel of four physiological relevant human CA isoforms, namely, the cytosolic isoforms hCA I and hCA II and the transmembrane tumor associated isoforms hCA IX and hCA XII. Pyridine indole-3-sulfonamide hybrids are selective inhibit transmembrane tumor associated isoforms hCA IX and hCA XII. However, all synthesized quinoline indole-3-sulfonamide hybrids have inhibitory effect on hCA IX isoforms, whereas few have shown inhibitory activity against hCA II and hCA XII as well. However, among all synthesized compound 6q and6p having good inhibitory activity against hCA IX with Ki 1.47 µM and 1.57 µM respectively.These quinoline/pyridine indole-3-sulfonamide conjugatesmay be regarded as potential leads for hCA IXselective inhibitors as anti-cancer agents.

Keywords: Acetazolamide; Carbonic anhydrases; Quinoline/pyridine indole-3-sulfonamide; Selective hCA IX inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm
  • Carbonic Anhydrase IX / metabolism
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Humans
  • Indoles / pharmacology
  • Isoenzymes
  • Neoplasms* / drug therapy
  • Pyridines
  • Quinolines* / pharmacology
  • Structure-Activity Relationship
  • Sulfonamides / pharmacology

Substances

  • Antigens, Neoplasm
  • Carbonic Anhydrase Inhibitors
  • Indoles
  • Isoenzymes
  • Pyridines
  • Quinolines
  • Sulfonamides
  • Carbonic Anhydrase IX