Andaç, Ahmet CenkÇakmak, OsmanÖkten, SalihÇağlar-Andaç, SenaIşıldak, İbrahim2021-12-272021-12-272021Andac, C. A., Cakmak, O., Okten, S., Caglar-Andac, S., & Isildak, I. (2021). In-silico Pharmacokinetic and Affinity Studies of Piperazine/Morpholine Substituted Quinolines in complex with GAK as promising anti-HCV agent. Journal of Computational Biophysics and Chemistry.2737-41652737-4173https://doi.org/10.1142/S273741652150054Xhttps://hdl.handle.net/20.500.12713/2345Piperazine/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.eninfo:eu-repo/semantics/closedAccessPiperazine/Morpholine Substituted QuinolineCyclin G Associated KinaseHepatitis C VirusMolecular DynamicsPharmacokineticMM-PBSAArticle208869879WOS:0007306033000082-s2.0-85121911896N/A10.1142/S273741652150054XQ4