Novel thiazolidinone-containing compounds, without the well-known sulphonamide zinc-binding group acting as human carbonic anhydrase IX inhibitors

Journal of Enzyme Inhibition and Medicinal Chemistry

Atilla Akdemir¹  Andrea Angeli²  Claudiu T. Supuran²  Kübra Demir³  Özlen Güzel-Akdemir³ 

[1] Computer-Aided Drug Discovery Laboratory, Department of Pharmacology, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turke;Department of NEUROFARBA, Sezione di Scienze Farmaceutiche Universita degli Studi di Firenze, Sesto Fiorentino, Florence, Italy;Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey;

关键词: carbonic anhydrase IX;    hCA IX;    thiazolidinone;    molecular modelling;    docking;   

DOI  :  10.1080/14756366.2018.1499628

来源: publisher

【 摘 要 】

A small collection of 26 structurally novel thiazolidinone-containing compounds, without the well-known sulphonamide zinc-binding group, were synthesised and tested in enzyme inhibition assays against the tumour-associated hCA IX enzyme. Inhibition constants in the lower micromolar region (KI < 25 μM) have been measured for 17 of the 26 compounds. Even though the KI values are relatively weak, the fact that they do not contain a sulphonamide moiety suggests that these compounds do not interact with the active site zinc ion. Therefore, docking studies and molecular dynamics simulations have been performed to suggest binding poses for these structurally novel inhibitors.

【 授权许可】

CC BY