Novel 2-substituted-benzimidazole-6-sulfonamides as carbonic anhydrase inhibitors: synthesis, biological evaluation against isoforms I, II, IX and XII and molecular docking studies

Journal of Enzyme Inhibition and Medicinal Chemistry

Alessandra Feoli¹  Sabrina Castellano¹  Ciro Milite¹  Alessandra Cipriano²  Ettore Novellino³  Elisabetta Barresi⁴  Sabrina Taliani⁴  Federico Da Settimo⁴  Sandro Cosconati⁵  Giorgio Amendola⁵  Claudiu T. Supuran⁶  Alessio Nocentini⁶  Silvia Bua⁶ 

[1] Department of Pharmacy, Epigenetic Med Chem Lab, University of Salerno, Fisciano (SA), Italy;Department of Pharmacy, Epigenetic Med Chem Lab, University of Salerno, Fisciano (SA), Italy;PhD Program in Drug Discovery and Development, University of Salerno, Fisciano (SA), Italy;Department of Pharmacy, University Federico II of Naples, Naples, Ital;Department of Pharmacy, Universy of Pisa, Pisa, Italy;DiSTABiF, Università della Campania Luigi Vanvitelli, Caserta, Italy;NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Sesto Fiorentino (Florence), Italy;

关键词: Carbonic anhydrase inhibitors;    benzimidazole-sulfonamides;    reduced flexibility approach;    isoform-selective inhibitors;    molecular docking;   

DOI  :  10.1080/14756366.2019.1666836

来源: publisher

【 摘 要 】

Inhibition of Carbonic Anhydrases (CAs) has been clinically exploited for many decades for a variety of therapeutic applications. Within a research project aimed at developing novel classes of CA inhibitors (CAIs) with a proper selectivity for certain isoforms, a series of derivatives featuring the 2-substituted-benzimidazole-6-sulfonamide scaffold, conceived as frozen analogs of Schiff bases and secondary amines previously reported in the literature as CAIs, were investigated. Enzyme inhibition assays on physiologically relevant human CA I, II, IX and XII isoforms revealed a number of potent CAIs, showing promising selectivity profiles towards the transmembrane tumor-associated CA IX and XII enzymes. Computational studies were attained to clarify the structural determinants behind the activities and selectivity profiles of the novel inhibitors.

【 授权许可】

CC BY