@article{
author = "Tomović, Katarina and Ilić, Budimir S. and Miljković, Marija and Dimov, Stefan and Yancheva, Denitsa and Kojić, Milan and Mavrova, Anelia T. and Kocić, Gordana and Smelcerović, Andrija",
year = "2019",
abstract = "A small library of benzo[4,5]thieno[2,3-d]pyrimidine phthalimide and amine derivatives was evaluated for inhibitory activity against dipeptidyl peptidase-4 (DPP-4). The phthalimide derivatives exhibited better activity than the amine precursors, with 2-(2-(3-chlorobenzyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)isoindoline-1,3-dione (compound 14) as the most effective inhibitor (IC50 = 34.17 +/- 5.11 mu M). The five most potent selected inhibitors did not show cytotoxicity to a greater extent on Caco-2 cells, even at a concentration of 250 mu M. Compound 14 is considered as a novel representative of the rare noncompetitive DPP-4 inhibitors. Molecular docking and dynamics simulation indicated the importance of the Tyr547, Lys554, and Trp629 residues of DPP-4 in the formation of the enzyme-inhibitor complex. These observations could be potentially utilized for the rational design and optimization of novel (structurally similar, with phthalimide moiety, or different) noncompetitive DPP-4 inhibitors, which are anyway rare, but favorable in terms of the saturation of substrate competition.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "Archiv Der Pharmazie",
title = "Benzo[4,5]thieno[2,3-d]pyrimidine phthalimide derivative, one of the rare noncompetitive inhibitors of dipeptidyl peptidase-4",
number = "1",
volume = "353",
doi = "10.1002/ardp.201900238"
}