In-silico pharmacokinetic and affinity studies of piperazine/morpholine substituted quinolines in complex with GAK as promising anti-HCV agent
Küçük Resim Yok
Tarih
2021
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
WORLD SCIENTIFIC PUBL CO PTE LTD
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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.
Açıklama
Anahtar Kelimeler
Piperazine/Morpholine Substituted Quinoline, Cyclin G Associated Kinase, Hepatitis C Virus, Molecular Dynamics, Pharmacokinetic, MM-PBSA
Kaynak
JOURNAL OF COMPUTATIONAL BIOPHYSICS AND CHEMISTRY
WoS Q Değeri
N/A
Scopus Q Değeri
Q4
Cilt
20
Sayı
8
Künye
Andac, 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.
