Design, synthesis, molecular modelling investigation and biological studies of novel human carbonic anhydrase inhibitors based on coumalic acid
Year: 2025
Type: article
Abstract: click chemistry have been performed. The synthesised compounds were tested for their inhibitory activities against hCA I, II, IX, and XII showing the lactone moiety to be crucial for inhibitory potency. Particularly, ester derivatives demonstrated selectivity for hCA IX and XII, with certain compounds exhibiting micromolar affinities. Notably, compound 8, featuring a bromine substitution, displayed the highest selectivity and potency against hCA IX and XII. Molecular docking studies further elucidated the binding mechanisms, revealing that the lactone ring hydrolysis plays a significant role in the inhibition process. These results offer valuable insights into the structure-activity relationships (SAR) of coumalic acid analogues and support their further biological investigation for cancer therapy by targeting hCA IX and XII.
Source: RSC Medicinal Chemistry
DOI: 10.1039/d5md00208g
Authors: Virginia Pontecorvi, Andrea Angeli, Luigi Cutarella, Mattia Mori, Daniela Secci, Michele Coluccia, Simone Carradori, Anna Troiani, Federico Pepi, Chiara Salvitti, Alessia Di Noi, Mattia Spano, Francesca Arrighi, Elena De Falco, Antonella Bordin, Emanuela Berrino, Arianna Granese, Paola Chimenti, Paolo Guglielmi, Claudiu T. Supuran
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funder: Fondazione Umberto Veronesi
OpenAlex ID: W4410894941