Synthesis, computational studies and assessment of in vitro inhibitory activity of umbelliferon-based compounds against tumour-associated carbonic anhydrase isoforms IX and XII

Journal of Enzyme Inhibition and Medicinal Chemistry

Andrea Angeli¹  Claudiu T. Supuran¹  Rosaria Gitto²  Francesca Mancuso²  Laura De Luca²  Sonia Del Prete³  Clemente Capasso³ 

[1] Dipartimento NEUROFARBA, Università di Firenze;Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali (CHIBIOFARAM), Università degli Studi di Messina;Istituto di Bioscienze e Biorisorse – CNR;

关键词: carbonic anhydrase inhibitors (cais);    tumour-associated ca isoforms;    coumarin;    pechmann condensation;    fries rearrangement;   

DOI  :  10.1080/14756366.2020.1786821

来源: DOAJ

【 摘 要 】

Coumarins are widely diffused secondary metabolites possessing a plethora of biological activities. It has been established that coumarins represent a peculiar class of human carbonic anhydrase (hCA) inhibitors having a distinct mechanism of action involving a non-classical binding with amino acid residues paving the entrance of hCA catalytic site. Herein, we report the synthesis of a small series of new coumarin derivatives 7-11, 15, 17 prepared via classical Pechmann condensation starting from resorcinol derivatives and suitable β-ketoesters. The evaluation of inhibitory activity revealed that these compounds possessed nanomolar affinity and high selectivity towards tumour-associated hCA IX and XII over cytosolic hCA I and hCA II isoforms. To investigate the binding mode of these new coumarin-inspired inhibitors, the most active compounds 10 and 17 were docked within hCA XII catalytic cleft.

【 授权许可】

Unknown