In-silico Pharmacokinetic and Affinity Studies of Piperazine/Morpholine Substituted Quinolines in Complex with GAK as Promising Anti-HCV Agent

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dc.authoridisildak, ibrahim/0000-0001-9654-1386
dc.authoridCAGLAR-ANDAC, Sena/0000-0002-4846-8310
dc.authoridOkten, Salih/0000-0001-9656-1803
dc.authoridAndac, Cenk A./0000-0002-9359-4295
dc.contributor.authorAndac, Cenk A.
dc.contributor.authorCakmak, Osman
dc.contributor.authorOkten, Salih
dc.contributor.authorCaglar-Andac, Sena
dc.contributor.authorIsildak, Ibrahim
dc.date.accessioned2025-01-21T16:41:49Z
dc.date.available2025-01-21T16:41:49Z
dc.date.issued2021
dc.departmentKırıkkale Üniversitesi
dc.description.abstractPiperazine/morpholine derivatives of quinoline substituted at positions C-3, C-6 and C-8 has been previously prepared by SNAr reactions of 3,6,8-tribromoquinoline (1) under microwave or conventional heating reaction conditions. In this study, we evaluated binding interactions between the piperazine/morpholine substituted quinolines and its highly-likely receptor, Cyclin G associated kinase (GAK) involved in hepatitis C virus (HCV) entry into host cells, via docking, molecular dynamics (MD), thermodynamic and pharmacokinetics computations in order to select a possible lead compound, which may be used for lead-optimization in our future studies to develop novel drug candidates against HCV infections. 372 nsec MD simulations followed by MM-PBSA thermodynamic computations revealed that compound 23 (K-d= 0.08nM) possesses the greatest potential to inhibit GAK. Pharmacokinetics computations suggest that compound 23 is a drug-like molecule as it conforms to the Lipinski filter. We determined that compound 23 could be a lead-like molecule for peripheric and cerebral HCV infections.
dc.identifier.doi10.1142/S273741652150054X
dc.identifier.endpage879
dc.identifier.issn2737-4165
dc.identifier.issn2737-4173
dc.identifier.issue8
dc.identifier.startpage869
dc.identifier.urihttps://doi.org/10.1142/S273741652150054X
dc.identifier.urihttps://hdl.handle.net/20.500.12587/24960
dc.identifier.volume20
dc.identifier.wosWOS:000730603300008
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.language.isoen
dc.publisherWorld Scientific Publ Co Pte Ltd
dc.relation.ispartofJournal of Computational Biophysics and Chemistry
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_20241229
dc.subjectPiperazine/morpholine substituted quinoline; Cyclin G associated kinase; Hepatitis C Virus; molecular dynamics; Pharmacokinetic; MM-PBSA
dc.titleIn-silico Pharmacokinetic and Affinity Studies of Piperazine/Morpholine Substituted Quinolines in Complex with GAK as Promising Anti-HCV Agent
dc.typeArticle

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