Synthesis and carbonic anhydrase inhibition of a series of SLC-0111 analogs

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Fabrizio Carta1, Daniela Vullo2, Sameh M Osman3

  • 1Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.

Bioorganic & Medicinal Chemistry
|March 29, 2017
PubMed

Insights

New sulfonamide analogs of SLC-0111 effectively inhibit tumor-associated carbonic anhydrase IX (CA IX). Some analogs show selectivity for CA IX/XII, offering potential for advanced cancer treatments by targeting hypoxic tumors and cancer stem cells.

Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Biochemistry

Background:

  • SLC-0111 is a carbonic anhydrase inhibitor (CAI) in clinical trials for advanced hypoxic tumors.
  • CA IX is a tumor-associated isoform crucial for tumor growth and metastasis.
  • CAI's antitumor effects include reducing cancer stem cells.

Purpose of the Study:

  • Synthesize and evaluate novel SLC-0111 analogs.
  • Investigate structure-activity relationships of new sulfonamide derivatives.
  • Identify potent and selective inhibitors of carbonic anhydrase IX and XII.

Main Methods:

  • Chemical synthesis of sulfanilamide and metanilamide analogs with varied substitutions.
  • In vitro assessment of carbonic anhydrase inhibitory activity.
  • Evaluation of selectivity profiles against CA IX and CA XII isoforms.

Main Results:

  • Sulfanilamide analogs demonstrated high efficacy as CA IX inhibitors.
  • Several sulfanilamide derivatives exhibited selective inhibition of CA IX/XII.
  • Metanilamide analogs were less effective against transmembrane CA isoforms.

Conclusions:

  • Novel sulfonamide derivatives show promise as targeted cancer therapeutics.
  • Tailored substitutions can yield potent and selective CA IX/XII inhibitors.
  • Structure-activity relationship analysis guides the development of next-generation CAIs.
Keywords:
Carbonic anhydraseInhibitorSLC-0111SulfonamideTumorUrea derivative

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