Handling drug-target selectivity: A study on ureido containing Carbonic Anhydrase inhibitors
Makaleler > Tam Makale · 2020
Yazarlar: Özlem AKGÜL, Srishti Singh, Jacob T. Andring, Robert McKenna, Silvia Selleri, Fabrizio Carta, Andrea Angeli, Claudiu T. Supuran
European Journal of Medicinal Chemistry, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2020, cilt 212, ss 113035-113035
DOI: 10.1016/j.ejmech.2020.113035
Özet
Here we report the synthesis of a series of taurine substituted sulfonamide derivatives 1-29 having the ureido moiety installed at the tail section as selective inhibitors of the tumor associated human (h) Carbonic Anhydrase (CA; EC 4.2.1.1) IX and XII. The series was deeply investigated for their kinetic features which demonstrated a strong dependence on the ureido moiety. High resolution X-ray crystallographic investigation on selected ligand adducts complexed with hCA II and hCA IX-mimic revealed a strong correlation between the ureido moiety and the amino acid residues Q92 and Q67 in both the hCA II and hCA IX-mimic, contributing to highly stabilized ligand-protein complex. (C) 2020 Elsevier Masson SAS. All rights reserved.