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Benzo[4,5]thieno[2,3-d]pyrimidine phthalimide derivative, one of the rare noncompetitive inhibitors of dipeptidyl peptidase-4
dc.creator | Tomović, Katarina | |
dc.creator | Ilić, Budimir S. | |
dc.creator | Miljković, Marija | |
dc.creator | Dimov, Stefan | |
dc.creator | Yancheva, Denitsa | |
dc.creator | Kojić, Milan | |
dc.creator | Mavrova, Anelia T. | |
dc.creator | Kocić, Gordana | |
dc.creator | Smelcerović, Andrija | |
dc.date.accessioned | 2023-09-26T08:28:23Z | |
dc.date.available | 2023-09-26T08:28:23Z | |
dc.date.issued | 2019 | |
dc.identifier.issn | 0365-6233 | |
dc.identifier.uri | https://imagine.imgge.bg.ac.rs/handle/123456789/1396 | |
dc.identifier.uri | http://intor.torlakinstitut.com/handle/123456789/700 | |
dc.description.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. | en |
dc.publisher | Wiley-V C H Verlag Gmbh, Weinheim | |
dc.relation | Faculty of Medicine of the University of Nis [4] | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/171025/RS// | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172044/RS// | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173019/RS// | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Technological Development (TD or TR)/31060/RS// | |
dc.rights | restrictedAccess | |
dc.source | Archiv Der Pharmazie | |
dc.subject | phthalimide | en |
dc.subject | noncompetitive DPP-4 inhibition | en |
dc.subject | molecular dynamics | en |
dc.subject | dipeptidyl peptidase-4 | en |
dc.title | Benzo[4,5]thieno[2,3-d]pyrimidine phthalimide derivative, one of the rare noncompetitive inhibitors of dipeptidyl peptidase-4 | en |
dc.type | article | |
dc.rights.license | ARR | |
dc.citation.issue | 1 | |
dc.citation.other | 353(1) | |
dc.citation.rank | M22 | |
dc.citation.volume | 353 | |
dc.identifier.doi | 10.1002/ardp.201900238 | |
dc.identifier.pmid | 31710123 | |
dc.identifier.scopus | 2-s2.0-85075069596 | |
dc.identifier.wos | 000495566900001 | |
dc.type.version | publishedVersion |