dc.creator | Kyriakis E., Karra A.G., Papaioannou O., Solovou T., Skamnaki V.T., Liggri P.G.V., Zographos S.E., Szennyes E., Bokor É., Kun S., Psarra A.-M.G., Somsák L., Leonidas D.D. | en |
dc.date.accessioned | 2023-01-31T08:47:40Z | |
dc.date.available | 2023-01-31T08:47:40Z | |
dc.date.issued | 2020 | |
dc.identifier | 10.1016/j.bmc.2019.115196 | |
dc.identifier.issn | 09680896 | |
dc.identifier.uri | http://hdl.handle.net/11615/75572 | |
dc.description.abstract | C-Glucopyranosyl imidazoles, thiazoles, and an N-glucopyranosyl tetrazole were assessed in vitro and ex vivo for their inhibitory efficiency against isoforms of glycogen phosphorylase (GP; a validated pharmacological target for the development of anti-hyperglycaemic agents). Imidazoles proved to be more potent inhibitors than the corresponding thiazoles or the tetrazole. The most potent derivative has a 2-naphthyl substituent, a Ki value of 3.2 µM for hepatic glycogen phosphorylase, displaying also 60% inhibition of GP activity in HepG2 cells, compared to control vehicle treated cells, at 100 μM. X-Ray crystallography studies of the protein – inhibitor complexes revealed the importance of the architecture of inhibitor associated hydrogen bonds or sulfur σ-hole bond interactions to Asn284 OD1, offering new insights to structure-based design efforts. Moreover, while the 2-glucopyranosyl-tetrazole seems to bind differently from the corresponding 1,2,3-triazole compound, the two inhibitors are equipotent. © 2019 Elsevier Ltd | en |
dc.language.iso | en | en |
dc.source | Bioorganic and Medicinal Chemistry | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85076026403&doi=10.1016%2fj.bmc.2019.115196&partnerID=40&md5=35b2a3588f3b971c8cb05e27585c4267 | |
dc.subject | 1,2,3 triazole derivative | en |
dc.subject | c beta dextro glucopyranosyl thiazole derivative | en |
dc.subject | glycogen phosphorylase | en |
dc.subject | hydrogen | en |
dc.subject | hyperglycemic agent | en |
dc.subject | imidazole derivative | en |
dc.subject | n beta dextro glucopyranosyl tetrazole | en |
dc.subject | thiazole derivative | en |
dc.subject | unclassified drug | en |
dc.subject | enzyme inhibitor | en |
dc.subject | glycogen phosphorylase | en |
dc.subject | hydrogen | en |
dc.subject | imidazole derivative | en |
dc.subject | sulfur | en |
dc.subject | tetrazole derivative | en |
dc.subject | thiazole derivative | en |
dc.subject | Article | en |
dc.subject | controlled study | en |
dc.subject | drug design | en |
dc.subject | drug potency | en |
dc.subject | drug structure | en |
dc.subject | drug synthesis | en |
dc.subject | drug targeting | en |
dc.subject | enzyme activity | en |
dc.subject | enzyme inhibition | en |
dc.subject | enzyme inhibitor complex | en |
dc.subject | ex vivo study | en |
dc.subject | Hep-G2 cell line | en |
dc.subject | human | en |
dc.subject | human cell | en |
dc.subject | hydrogen bond | en |
dc.subject | in vitro study | en |
dc.subject | X ray crystallography | en |
dc.subject | chemical structure | en |
dc.subject | chemistry | en |
dc.subject | dose response | en |
dc.subject | metabolism | en |
dc.subject | molecular model | en |
dc.subject | structure activity relation | en |
dc.subject | synthesis | en |
dc.subject | Crystallography, X-Ray | en |
dc.subject | Dose-Response Relationship, Drug | en |
dc.subject | Drug Design | en |
dc.subject | Enzyme Inhibitors | en |
dc.subject | Glycogen Phosphorylase, Liver Form | en |
dc.subject | Hep G2 Cells | en |
dc.subject | Humans | en |
dc.subject | Hydrogen | en |
dc.subject | Imidazoles | en |
dc.subject | Models, Molecular | en |
dc.subject | Molecular Structure | en |
dc.subject | Structure-Activity Relationship | en |
dc.subject | Sulfur | en |
dc.subject | Tetrazoles | en |
dc.subject | Thiazoles | en |
dc.subject | Elsevier Ltd | en |
dc.title | The architecture of hydrogen and sulfur σ-hole interactions explain differences in the inhibitory potency of C-β-D-glucopyranosyl thiazoles, imidazoles and an N-β-D glucopyranosyl tetrazole for human liver glycogen phosphorylase and offer new insights to structure-based design | en |
dc.type | journalArticle | en |