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

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

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: hani.noha@gmail.com.
  • 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: claudiu.supuran@unifi.it.
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.

Figures