The anticancer therapeutic potential of pyrimidine-sulfonamide hybrids

Future Med Chem. 2024;16(9):905-924. doi: 10.4155/fmc-2024-0010. Epub 2024 Apr 16.

Abstract

Cancer as a devastating malignancy, seriously threatens human life and health, but most chemotherapeutics have long been criticized for unsatisfactory therapeutic efficacy due to drug resistance and severe off-target toxicity. Pyrimidines, including fused pyrimidines, are privileged scaffolds for various biological cancer targets and are the most important class of metalloenzyme carbonic anhydrase inhibitors. Pyrimidine-sulfonamide hybrids can act on different targets in cancer cells simultaneously and possess potent activity against various cancers, revealing that hybridization of pyrimidine with sulfonamide is a promising approach to generate novel effective anticancer candidates. This review aims to summarize the recent progress of pyrimidine-sulfonamide hybrids with anticancer potential, covering papers published from 2020 to present, to facilitate further rational design of more effective candidates.

Keywords: cancer; hybrid molecules; mechanisms of action; pyrimidine; quinazoline; structure–activity relationship; sulfonamide.

Plain language summary

[Box: see text].

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Humans
  • Molecular Structure
  • Neoplasms* / drug therapy
  • Neoplasms* / pathology
  • Pyrimidines* / chemical synthesis
  • Pyrimidines* / chemistry
  • Pyrimidines* / pharmacology
  • Sulfonamides* / chemical synthesis
  • Sulfonamides* / chemistry
  • Sulfonamides* / pharmacology

Substances

  • Sulfonamides
  • Pyrimidines
  • Antineoplastic Agents
  • Carbonic Anhydrase Inhibitors
  • pyrimidine