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

Andac C. A., Cakmak O., Okten S., Caglar-Andac S., IŞILDAK İ.

JOURNAL OF COMPUTATIONAL BIOPHYSICS AND CHEMISTRY, vol.20, no.08, pp.869-879, 2021 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 20 Issue: 08
  • Publication Date: 2021
  • Doi Number: 10.1142/s273741652150054x
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.869-879
  • Keywords: Piperazine/morpholine substituted quinoline, Cyclin G associated kinase, Hepatitis C Virus, molecular dynamics, Pharmacokinetic, MM-PBSA, MOLECULAR-DYNAMICS, FORCE-FIELD, DERIVATIVES, INHIBITORS, ACCURACY, OPTIMIZATION, SIMULATIONS, GEFITINIB, PROTEINS, ENZYMES
  • Yıldız Technical University Affiliated: Yes


Piperazine/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.