2. Academic Validation
  3. Design, synthesis & biological evaluation of ferulic acid-based small molecule inhibitors against tumor-associated carbonic anhydrase IX

Design, synthesis & biological evaluation of ferulic acid-based small molecule inhibitors against tumor-associated carbonic anhydrase IX

  • Bioorg Med Chem. 2020 May 1;28(9):115424. doi: 10.1016/j.bmc.2020.115424.
Babita Aneja 1,  Aarfa Queen 2,  Parvez Khan 3,  Farheen Shamsi 4,  Afzal Hussain 5,  Phool Hasan 4,  M Moshahid A Rizvi 4,  Constantin G Daniliuc 6,  Mohamed F Alajmi 5,  Mohd Mohsin 4,  Md Imtaiyaz Hassan 7,  Mohammad Abid 8
Affiliations

Affiliations

  • 1 Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India; Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
  • 2 Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India; Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
  • 3 Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
  • 4 Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
  • 5 Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
  • 6 Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, 48149, Germany.
  • 7 Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. Electronic address: mihassan@jmi.ac.in.
  • 8 Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. Electronic address: mabid@jmi.ac.in.
PMID: 32209296 DOI: 10.1016/j.bmc.2020.115424
Abstract

Carbonic Anhydrase IX (CAIX) is an emerging drug target for hypoxia associated cancers. To identify potent and selective inhibitors of CAIX, a small library of ferulic acid (FA) derivatives bearing triazole moiety has been designed, synthesized and evaluated against different human CA isoforms (CAII, CAVA & CAIX). Though most of the compounds showed CAIX inhibition in the micromolar range, compound 7i selectively inhibits CAIX in the nanomolar range (IC50 = 24 nM). In silico analysis revealed binding of 7i with the catalytically important amino acid residues of CAIX. Further, cell-based studies indicate that 7i inhibits the activity of CAIX, decreases the epithelial to mesenchymal transitions, induces Apoptosis, inhibits cell migration and colonization potential of Cancer cells. Taken together, these results emphasized the use of 7i as a prospective pharmacological lead molecule in CAIX targeted Anticancer therapeutics.

Keywords

Anticancer; Apoptosis; Carbonic anhydrase IX (CAIX) inhibitors; Ferulic acid.

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