2. Academic Validation
  3. Synthesis, carbonic anhydrase inhibition and cytotoxic activity of novel chromone-based sulfonamide derivatives

Synthesis, carbonic anhydrase inhibition and cytotoxic activity of novel chromone-based sulfonamide derivatives

  • Eur J Med Chem. 2015:96:425-35. doi: 10.1016/j.ejmech.2015.04.033.
Fadi M Awadallah 1,  Tamer A El-Waei 2,  Mona M Hanna 2,  Safinaz E Abbas 2,  Mariangela Ceruso 3,  Beyza Ecem Oz 4,  Ozen Ozensoy Guler 4,  Claudiu T Supuran 5
Affiliations

Affiliations

  • 1 Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini Street, 11562, Cairo, Egypt. Electronic address: fadi_mae@hotmail.com.
  • 2 Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini Street, 11562, Cairo, Egypt.
  • 3 University of Florence, Neurofarba Department, Via Ugo Schiff 6, Polo Scientifico, 50019, Sesto Fiorentino, Firenze, Italy.
  • 4 University of Florence, Neurofarba Department, Via Ugo Schiff 6, Polo Scientifico, 50019, Sesto Fiorentino, Firenze, Italy; Yildirim Beyazit University Faculty of Medicine, Department of Medical Biology, Cinnah Campus, Ankara, Turkey.
  • 5 University of Florence, Neurofarba Department, Via Ugo Schiff 6, Polo Scientifico, 50019, Sesto Fiorentino, Firenze, Italy. Electronic address: claudiu.supuran@unifi.it.
PMID: 25912674 DOI: 10.1016/j.ejmech.2015.04.033
Abstract

Four series of sulfonamides incorporating chromone moieties were synthesized and assessed for their cytotoxic activity against MCF-7 and A-549 cell lines, considering the fact that some of these tumors overexpress isoforms of Carbonic Anhydrase (CA, EC 4.2.1.1) which is inhibited by sulfonamides. Most new sulfonamides showed weak inhibitory activity against the offtarget, cytosolic isoforms hCA I, II but effectively inhibited the tumor-associated hCA IX and XII. The most active compounds featured a primary SO2NH2 group and were active in the low micromolar range against MCF-7 and A-549 cell lines. Compound 4a showed IC50 of 0.72 and 0.50 μM against MCF-7 and A-549 cell lines, respectively, and was further evaluated for its proapoptotic activity which proved enhanced in both tumor types.

Keywords

Breast cancer; Carbonic anhydrase; Chromone; Lung cancer; Sulfonamide.

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