Furagin Derivatives-Nitrofuran-Based Hydrazones as Potential Dual Inhibitors of Thioredoxin Reductase and Carbonic

Related Experiment Video

Updated: Jul 10, 2026

NMR-Based Activity Assays for Determining Compound Inhibition, IC50 Values, Artifactual Activity, and Whole-Cell Activity of Nucleoside Ribohydrolases
10:24

NMR-Based Activity Assays for Determining Compound Inhibition, IC50 Values, Artifactual Activity, and Whole-Cell Activity of Nucleoside Ribohydrolases

Published on: June 30, 2019

Aleksandrs Pustenko1, Raitis Bobrovs2, Katrīna Freimane2

  • 1Latvian Institute of Organic Synthesis, Riga, Latvia.

Chemmedchem
|July 8, 2026
PubMed

Insights

New furagin derivatives show promise as dual inhibitors of thioredoxin reductase (TrxR) and cancer-associated carbonic anhydrases (CA IX/XII). Compound 7g demonstrated potent TrxR inhibition, suggesting a novel therapeutic strategy for cancer treatment.

Area of Science:

  • Medicinal Chemistry
  • Biochemistry
  • Oncology

Background:

  • Cancer is a leading cause of death globally, necessitating novel therapeutic strategies.
  • Dual inhibition of thioredoxin reductase (TrxR) and carbonic anhydrase (CA) isoforms IX and XII offers a promising approach for selective cancer therapy.
  • Furagin, an antibacterial agent, has shown potential as a CA inhibitor, but its TrxR inhibitory activity is unexplored.

Purpose of the Study:

  • To design and synthesize novel furagin derivatives as potential dual inhibitors of TrxR and cancer-associated CA isoforms.
  • To evaluate the inhibitory activity of these derivatives against human CA isoforms (hCA I, hCA II, hCA IX, hCA XII) and rat TrxR1 (rTrxR1).

Main Methods:

  • Synthesis of a series of nitrofuran-based hydrazone derivatives (7a-7s).
  • Assay of carbonic anhydrase inhibition using a stopped-flow CO2 hydration assay.
  • Assessment of rTrxR1 inhibition using a 5,5'-Dithiobis(2-nitrobenzoic acid) (DTNB) reduction assay.

Main Results:

  • Most derivatives showed weak activity against cytosolic hCA I and hCA II.
  • Compounds exhibited moderate and selective inhibition of cancer-associated hCA IX and hCA XII, with notable activity against hCA XII.
  • Several derivatives inhibited rTrxR1, with compound 7g being the most potent (IC50 = 11 μM).

Conclusions:

  • The synthesized furagin derivatives demonstrate potential as dual inhibitors of TrxR and cancer-associated CA isoforms.
  • Compound 7g is identified as a potent inhibitor of rTrxR1.
  • These findings support the development of novel anticancer agents targeting both redox homeostasis and pH regulation in cancer cells.
Keywords:
antitumor agentscancer‐related isoformscarbonic anhydrase inhibitorsdual inhibitorsthioredoxin reductase inhibitors

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