Novel sulfonamides bearing pyrrole and pyrrolopyrimidine moieties as carbonic anhydrase inhibitors: Synthesis, cytotoxic activity and molecular modeling

作者：Ghorab Mostafa M^*; Ceruso Mariangela; Alsaid Mansour S; Nissan Yassin M; Arafa Reem K; Supuran Claudiu T

来源：European Journal of Medicinal Chemistry, 2014, 87: 186-196.

DOI：10.1016/j.ejmech.2014.09.059

• Pyrroles
• Pyrrolopyrimidines
• Sulfonamides
• Carbonic anhydrase
• Cytotoxic activity

Novel pyrrole and pyrrolopyrimidine scaffold-based sulfonamides were designed and synthesized. The carbonic anhydrase (CA) inhibition ability of all derivatives was assessed against the human (h) cytosolic isoforms hCA I and II and the transmembrane, tumor-associated isoforms hCA IX and XII. Some of these sulfonamides were 6-8 fold more potent than the reference drug acetazolamide (AZA, K-i = 5.7 nM)) against hCA XII showing subnanomolar activity. The in vitro cytotoxicity of these derivatives was evaluated against MCF-7, where some derivatives were more cytotoxic than doxorubicin (IC50 = 8.02 mu M) displaying IC50 values between 6.46 and 7.56 mu M. Docking of these sulfonamides with CA XII was performed and their binding modes were comparable with that of AZA.

• 出版日期2014-11-24