Evaluation of analogues of furan-amidines as inhibitors of NQO2

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Soraya Alnabulsi
  • Buthaina Hussein
  • Elham Santina
  • Izzeddin Alsalahat
  • Manikandan Kadirvel
  • Rachael N. Magwaza
  • Carl H. Schwalbe
  • Alex G. Baldwin


Inhibitors of the enzyme NQO2 (NRH: quinone oxidoreductase 2) are of potential use in cancer chemotherapy and malaria. We have previously reported that non-symmetrical furan amidines are potent inhibitors of NQO2 and here novel analogues are evaluated. The furan ring has been changed to other heterocycles (imidazole, N-methylimidazole, oxazole, thiophene) and the amidine group has been replaced with imidate, reversed amidine, N-arylamide and amidoxime to probe NQO2 activity, improve solubility and decrease basicity of the lead furan amidine. All compounds were fully characterised spectroscopically and the structure of the unexpected product N-hydroxy-4-(5-methyl-4-phenylfuran-2-yl)benzamidine was established by X-ray crystallography. The analogues were evaluated for inhibition of NQO2, which showed lower activity than the lead furan amidine. The observed structure-activity relationship for the furan-amidine series with NQO2 was rationalized by preliminary molecular docking and binding mode analysis. In addition, the oxazole-amidine analogue inhibited the growth of Plasmodium falciparum with an IC50 value of 0.3 μM.

Bibliographical metadata

Original languageEnglish
JournalBioorganic & medicinal chemistry letters
Early online date12 Mar 2018
Publication statusPublished - 2018

Related information