Synthesis of 4-(thiazol-2-ylamino)-benzenesulfonamides with carbonic anhydrase I, II and IX inhibitory activity and cytotoxic effects against breast cancer cell lines

  • Bioorg Med Chem. 2016 Jul 1;24(13):3043-3051. doi: 10.1016/j.bmc.2016.05.016.
Nagwa M Abdel Gawad  1 ,  Noha H Amin  2 ,  Mohammed T Elsaadi  3 ,  Fatma M M Mohamed  3 ,  Andrea Angeli  4 ,  Viviana De Luca  5 ,  Clemente Capasso  5 ,  Claudiu T Supuran  6
Affiliations
  • 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
  • 2. Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt. Electronic address: [email protected].
  • 3. Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
  • 4. Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
  • 5. Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy.
  • 6. Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: [email protected].
PMID: 27234893 DOI: 10.1016/j.bmc.2016.05.016
Abstract

A series of 4-(thiazol-2-ylamino)-benzenesulfonamides was synthesized and screened for their Carbonic Anhydrase (CA, EC 4.2.1.1) inhibitory and cytotoxic activity on human breast Cancer cell line MCF-7. Human (h) CA isoforms I, II and IX were included in the study. The new sulfonamides showed excellent inhibition of all three isoforms, with KIs in the range of 0.84-702nM against hCA I, of 0.41-288nM against hCA II and of 5.6-29.2 against the tumor-associated hCA IX, a validated anti-tumor target, with a sulfonamide (SLC-0111) in Phase I clinical trials for the treatment of hypoxic, metastatic solid tumors overexpressing CA IX. The new compounds showed micromolar inhibition of growth efficacy against breast Cancer MCF-7 cell lines.

Keywords
Antitumor; Carbonic anhydrase; Cytotoxic agent; Inhibitor; Sulfonamide.