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

Abdel Gawad, Nagwa M.; Amin, Noha H.; Elsaadi, Mohammed T.; Mohamed, Fatma M. M.; Angeli, Andrea; De Luca, Viviana; Capasso, Clemente; Supuran, CLAUDIU TRANDAFIR

doi:10.1016/j.bmc.2016.05.016

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.

Synthesis of 4-(thiazol-2-ylamino)-benzenesulfonamides with carbonic anhydrase I, II and IX inhibitory activity and cytotoxic effects against breast cancer cell lines / Abdel Gawad, Nagwa M.; Amin, Noha H.; Elsaadi, Mohammed T.; Mohamed, Fatma M.M.; Angeli, Andrea; De Luca, Viviana; Capasso, Clemente; Supuran, Claudiu T. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 24:(2016), pp. 3043-3051. [10.1016/j.bmc.2016.05.016]