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Updated: Jun 29, 2025

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
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Novel 1,2,4-triazoles as selective carbonic anhydrase inhibitors showing ancillary anticathepsin B activity

Amit Kumar1, Priyanka Arya1, Simone Giovannuzzi2

  • 1Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana, 136119, India.

Future Medicinal Chemistry
|April 4, 2024
PubMed

Insights

Novel 1,2,4-triazole derivatives effectively inhibit cancer-related human carbonic anhydrase (hCA) IX and XII, alongside cathepsin B. These compounds show promise for developing targeted cancer therapies.

Area of Science:

  • Medicinal Chemistry
  • Biochemistry
  • Cancer Research

Background:

  • Targeting cancer often involves a multi-target approach.
  • Human carbonic anhydrase (hCA) IX and XII, and cathepsin B are key cancer targets.
  • Developing selective inhibitors for these targets is crucial.

Purpose of the Study:

  • To synthesize and evaluate novel 1,2,4-triazole derivatives.
  • To assess their inhibitory potential against hCA I, II, IX, XII, and cathepsin B.
  • To explore a multi-target strategy for cancer therapy.

Main Methods:

  • Synthesis of 22 novel 1,2,4-triazole derivatives.
  • In vitro enzyme inhibition assays for hCA isoforms and cathepsin B.
  • Molecular modeling studies to support experimental findings.

Main Results:

  • Compounds showed potent inhibition against hCA IX and/or XII.
  • High selectivity was observed over off-target hCA I and II isoforms.
  • Significant anticathepsin B activity was demonstrated at low concentrations (10-7 M).
  • In vitro results were corroborated by molecular modeling.

Conclusions:

  • The synthesized compounds are effective dual inhibitors of hCA IX/XII and cathepsin B.
  • These findings provide a basis for designing novel cancer therapeutics.
  • The study highlights the potential of 1,2,4-triazole derivatives in multi-target cancer therapy.
Keywords:
1,2,4-triazolebenzenesulfonamidecancercarbonic anhydrase inhibitorscathepsin B inhibitorstail-approach

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