Synthesis, activatory effects, molecular docking and ADME studies as rabbit muscle pyruvate kinase activators of ureido phenyl substituted 1,4-dihydropyridine derivatives

Basit Öğe Kaydı
dc.authoridOzdemir, Oguzhan/0000-0002-9588-3285
dc.authoridCALISIR, Umit/0000-0001-7699-2008
dc.authoridDemirci, Tuna/0000-0001-8933-4944
dc.authoridARSLAN, Mustafa/0000-0003-0796-4374
dc.authoridKAYA, Mustafa Oguzhan/0000-0002-8592-1567
dc.contributor.authorKaya, Mustafa Oguzhan
dc.contributor.authorDemirci, Tuna
dc.contributor.authorCalisir, Umit
dc.contributor.authorOzdemir, Oguzhan
dc.contributor.authorKaya, Yesim
dc.contributor.authorArslan, Mustafa
dc.date.accessioned2024-12-24T19:24:45Z
dc.date.available2024-12-24T19:24:45Z
dc.date.issued2024
dc.departmentSiirt Üniversitesi
dc.description.abstractIn this study, the activation of pyruvate kinase enzyme in vitro via different urea substituents in the para position as functional groups of 1,4-dihydropyridine derivatives synthesized by Hantzsch reaction method was investigated. Elemental analysis, 1H-NMR, 13C-NMR and FT-IR spectroscopy were used to identify the ureido phenyl substituted 1,4-dihydropyridine derivatives. Virtual screening based on molecular docking supported the results of possible in vitro pyruvate kinase (PK) activators among the synthesized substances. The results showed that all compounds successfully activated PK. The strongest activator effect was shown by ethyl-4-(4-(4-(3-(3-methoxyphenyl)thioureido)phenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,7,8-hexahydroquinolin-3 (7) with an AC50 value of 87.70 mu M. In molecular docking studies, full compatibility (- 3016.93 FF), binding affinities (Delta G = - 8.58 kcal/mol), LUMO-HOMO energy gap (Delta E = 7.85 eV) in Density functional theory (DFT) studies and drug similarity score of the compounds were found to be 0.69. These results shed light on the therapeutic potential of the produced compounds to treat PK-related diseases.
dc.identifier.doi10.1007/s11164-023-05149-6
dc.identifier.endpage463
dc.identifier.issn0922-6168
dc.identifier.issn1568-5675
dc.identifier.issue1
dc.identifier.scopus2-s2.0-85174293248
dc.identifier.scopusqualityQ2
dc.identifier.startpage437
dc.identifier.urihttps://doi.org/10.1007/s11164-023-05149-6
dc.identifier.urihttps://hdl.handle.net/20.500.12604/6127
dc.identifier.volume50
dc.identifier.wosWOS:001084606000001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofResearch on Chemical Intermediates
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_20241222
dc.subject1,4-dihydropyridine
dc.subjectPyruvate kinase
dc.subjectCancer
dc.subjectUrea
dc.subjectHantzsch reaction
dc.titleSynthesis, activatory effects, molecular docking and ADME studies as rabbit muscle pyruvate kinase activators of ureido phenyl substituted 1,4-dihydropyridine derivatives
dc.typeArticle

Dosyalar

Koleksiyon

WOS İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu